Research on machine learning-based activity prediction models for KRAS inhibitors / 中国药科大学学报

@#Abstract: Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is one of the most commonly mutated oncogenes. It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation. In this study, machine learning was applied to develop a QSAR(quantitative structure-activity relationship) model for KRAS small molecule inhibitors. A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system) for KRAS inhibitors were collected from three databases: ChEMBL, BindingDB, and PubChem. And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models, namely, random forest, support vector machine, and extreme gradient boosting machine. The results showed that the SVM model combined with mutual information feature selection exhibited the best performance: AUCtest=0.912, ACCtest=0.859, F1test=0.890. Moreover, it also demonstrated good predictive performance on the external validation set(AUCExt=0.944, RecallExt=0.856, FPRExt=0.111). This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

Expression of optineurin in multiple myeloma and its clinical significance / 西安交通大学学报(医学版)

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Mechanism of astragaloside Ⅳ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway / 中国中药杂志

This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Respiratory infectious diseases and tissue "damage-repair" balance:pathological characteristics, treatment, and characteristics of traditional Chinese medicine / 中国中药杂志

Respiratory infectious diseases are important diseases causing major public safety events, posing a great threat to life, health, and social development. Effective control and scientific treatment of the diseases is the key basis for ensuring the stability and long-term development of the community of a shared future for human health. Although the pathogens of respiratory viral infectious diseases are diverse and the process is complex, the common pathological basis of their pathogenesis is characterized by the "damage-repair" functional imbalance of the immune microenvironment of the lesions, which leads to the subsequent structural and functional destruction of important organs. Therefore, the treatment should focus on antivirus and immunological regulation, strengthen the protection against immune injury, and promote the functional repair of damaged tissues. The above conclusions are the scientific core of host-directed therapies(HDT), which coincides with "human-disease co-treatment and healthy qi and pathogen interaction" in traditional Chinese medicine(TCM) theories. Under the support of TCM and western medicine theories, the complete pathological chain "infection-immunity-injury" of respiratory viral infectious diseases is integrated with dynamic change in "healthy qi-pathogen" in TCM to transform the treatment focus from the diseases to the patients. It is possible to fundamentally correct the "damage-repair" imbalance in the disease state, change the environment for disease development, and bring benefits to patients by strengthening human intervention, maintaining immune homeostasis, enhancing the protection of tissues and organs, and promoting the repair and regeneration of damaged tissues. This study focused on the common and key pathological processes of respiratory infectious diseases, especially the immune damage caused by the viral infection, to seek effective prevention and treatment strategies, review relevant theoretical progress, summarize effective drug candidates, prospect future research and development, and highlight the therapeutic characteristics of TCM.

Current drug research on intestinal mucosal healing in inflammatory bowel disease based on macrophage regulation / 药学学报

Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.

Research progress on quality and efficacy evaluation of Rehmanniae Radix Praeparata based on pharmacodynamic material basis / 中草药

The chemical constituents, pharmacological action of active components, and processing of Rehmanniae Radix Praeparata were reviewed in this study to explain its pharmacodynamic material basis and explore the quality and efficacy evaluation of Rehmanniae Radix Praeparata with different processing degrees from the view of the whole. This paper is expected to reveal the scientific connotation of processing, providing new research ideas for the quality and efficacy evaluation and the determination of the possessing end-point of Rehmanniae Radix Praeparata.

Clinical efficacy and safety of Apatinib in the treatment of advanced esophageal cancer in elderly patients / 中华老年医学杂志

Objective To investigate the clinical efficacy and safety of Apatinib in treating the advanced esophageal cancer and their prognosis in elderly patients.Methods Totally 52 elderly patients with advanced esophageal cancer who met the inclusion and exclusion criteria at our hospital from March 2015 to August 2017 were retrospectively enrolled.They were treated with Apatinib.The clinical efficacy,adverse reactions and influencing factors for the prognosis were analyzed.Results The partial remission rate(PRR) was 25.0％ and the disease control rate(DCR)was 71.2％ in 52 patients.The main adverse reactions were hypertension,hand-foot syndrome and proteinuria,with the incidence of 50.0％,38.5％ and 36.5％,respectively.The degree of adverse reactions was mainly grade 1 ～ 2.The median progression-free survival(PFS)was 3.8 months,and the median overall survival(OS)was 7.0 months.Univariate analysis (log-rank test) indicated that the degree of adverse reactions(x2 =5.075,P =0.024) and the Eastern Cooperative Oncology Group (ECOG) score (x2 =7.550,P =0.006)were associated with OS in elderly patients with advanced esophageal cancer.Cox multivariate regression analysis showed that the degree of adverse reactions(HR =1.963,P =0.045)and ECOG score(HR =0.458,P =0.015)were the independent influencing factors for OS in elderly patients with advanced esophageal cancer.Conclusions Due to mild adverse reactions and a high safety,Apatinib still has a certain clinical efficacy in the treatment of elderly patients with advanced esophageal cancer.Moreover,patients with the low ECOG score and high degree of adverse reactions have better prognosis.

Molecular mechanism of vascular remodeling in hypertension and Chinese medicine intervention / 生理学报

Vascular remodeling is a significant pathological characteristic of hypertension, which is regulated by complex regulatory networks. The vascular remodeling may be adaptive initially, however it becomes maladaptive and decompensation eventually and further compromises target organ function, leading to hypertensive cardiovascular complications. This review focuses on the role and mechanisms of vascular remodeling in the pathogenesis and progression of hypertension and its complications. Moreover, the strategies of syndrome differentiation of traditional Chinese medicine application provide clinical and theoretical evidences for hypertensive vascular remodeling therapy. A better understanding of underlying signaling pathways, therapeutic targets in vascular remodeling, as well as screening of active ingredients from traditional Chinese medicine may be able to provide some effective approaches for vascular protection in hypertensive diseases.

Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice / 中国药理学通报

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

EGCG ameliorating learning and memory impairment in APP/PS1 mice by inhibiting p75 NTR pathway / 中国药理学通报

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.

Combination of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging is an optimal way to evaluate rheumatoid arthritisin rats dynamically / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Many methods have been used to observe the progress of RA. The purpose of this study was to observe the progress of RA in rats with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the relationships among different methods in evaluation of RA.</p><p><b>METHODS</b>Sixteen healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA group and a control group. Bovine type II emulsified incomplete Freud's adjuvant was used to induce arthritis in the RA group. Arthritis score of the rats in two groups were recorded, and (18)F-FDG PET/CT, MR imaging were performed both on the corresponding rats every 3 days. All the rats were sacrificed at week 5, and histopathological examination was performed on rat knees stained with haematoxylin and eosin.</p><p><b>RESULTS</b>The arthritis score and the standard uptake value (SUV) of knee joints in RA rats increased with the progression of arthritis gradually. Both peaks of arthritis score and SUV appeared at 21 days after the first immune injection, then the arthritis score and SUV of knee joints decreased slowly. The arthritis scores of knee joints in RA rats were positively correlated with their SUV changes. The MR images were confirmed by the histopathological studies.</p><p><b>CONCLUSION</b>PET/CT can detect the earliest molecular metabolism changes of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all of which indicated that PET/CT and MR imaging may be applied as useful tools to monitor the progress of RA.</p>

Expression of integrin linked kinase in retina with oxygen-induced retinopathy / 中华实验眼科杂志

BackgroundIt has been well-known that integrin linked kinase(ILK) plays an important role in the pathogenesis of neorascularization.But there are few researches to elucidate the relationship between ILK and retinal nevascularization. Objective This study was to explore the expression and significance of ILK on retinal neovascularization and new vessels regression in the oxygen-induced retinopathy(OIR) mouse model. Methods One hundred and twenty-eight 7-day-old C57BL/6J mice were randomly divided into the normal group and model group.The mice were rose in(75±2)％O2 environment with mother mice together for 5 days and then in normal environment for 5 days to establish the OIR models.The mice in normal group were rose in the normal environment for 21 days.The 17-day-old mice were sacrificed and retinal sections were prepared for histopathological examination and the numbers of the cellular nuclei of vascular endotheliumbreaking retinalinternal limiting membranewere calculated.Retinal sections and sheeting were prepared in 12,14,17 and 21 -day-old mice to examine the formation and regression of new blood vessel using ADP histochemistry staining,and then immunochemistry,real-time PCR and Western-blotting were used to detect the expressions of ILK and its mRNA in retina. ResultsThe numbers of the cellular nuclei of vascular endothelium breaking retinal internal limiting membrane were (45.64 ± 12.17 )in OIR group,and those of the normal group were( 0.35±0.14 )with a significant difference between two groups (t =22.85,P＜0.05).Retinal new blood vessel appeared in 14-day mice,and peaked in 17-day mice and then regression in 21-day mice.ILK protein was expressed mainly in retinal ganglion cell layer,inner nuclear layer,inner plexiform layer and photoreceptor layer.Real-time PCR showed that ILK mRNA expressing levels in retina in model group were( 1.00±0.22),(1.85±0.17),(1.58±0.43) and(1.53±0.36) respectively in 12-,14-,17- and 21-day mice.Westernblotting determined that the A value of the ILK/β-actin was increased in 12-,14-,17-day mice and decreased in 21-day mice,and the A values were significantly higher in model group than the control group in various aged mice ( t =2.97,P＜0.05 ;t =11.88,P＜0.01 ;t =16.84,P＜0.01 ;t =13.00,P＜0.01 ). ConclusionsThese results indicate a space-time corresponding relation between the expression of ILK and retinal neovascularization.The obvious positive expression of ILK may be highly correlated with retinal neovascularization.

Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis.</p><p><b>METHODS</b>Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II.</p><p><b>RESULTS</b>The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen.</p><p><b>CONCLUSION</b>This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.</p>

Magnetic resonance urography and X-ray urography findings of congenital megaureter / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To observe the imaging findings of congenital megaureter in order to enhance the understanding of this disease.</p><p><b>METHODS</b>Image data of 5 patients with congenital megaureter and 2 misdiagnosed patients were analyzed, and image findings of congenital megaureter were summarized.Elscint Prestig 2.0T superconductive magnetic resonance urography (MRU) with conventional sequence (spin-echo, T1WI560 ms/16 ms; fast spin-echo, T2WI 9600 ms/96 ms ) was performed. Raw data were acquired with fastspin-echo sequence from heavy T2-weighted image (9600 ms/120 ms). Post-processing method of MRU was the maximum intensity projection with three-dimensional reconstruction in the workstation. Intravenous pyelography (IVP) was conducted, in which X-rayfilms were taken 7 minutes, 15 minutes, and 30 minutes after injecting contrast agent, exceptthat in 2 patients the films were taken delayed at 60 and 90 minutes .X-ray retrograde pyelography was performed on 2 patients, successful in one butfailed in the other.</p><p><b>RESULTS</b>The dilated ureter showed hypointensity on T1-weighted images and hyperintensity on T2-weighted images in conventional MRI. The mass wall was intact, uniform in thickness, and showing hypointensity on T1-weighted and T2-weighted images. The MRU images showed a retroperitoneal mass appearing as an elongated tubular cystic structure spreading from kidney to bladder. MRU also revealed dilated calices and renal pelvis, pelviureteric obstruction, and renal duplication. The main signs of congenital megaureter in X-urography was significant dilatation of ureter, or normal renal pelvis with ureter dilatation, hydronephrosis, deformity, and displacement.</p><p><b>CONCLUSIONS</b>MRU with X-urography could visualizethe characteristics of congenital megaureter, including the dilation of renal pelvis and ureter, calculi, urinary tract duplication, and stenosis location. The two techniques can complement each other in disease diagnosis and provide more detailed information for preoperative treatment.</p>

Effect of amygdalin on serum proteinic biomarker in pulmonary fibrosis of bleomycin-induced rat / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate effect of amygdalin on expression of four biomarkers in the animal model of pulmonary fibrosis induced by bleomycin.</p><p><b>METHODS</b>Rats were given one dose (5 mg/kg) of bleomycin in bleomycin-treated groups, amygdalin-treated groups and saline in controls by intratracheal instillation exposed surgically. The amygdalin-treated groups rats were treated with intraperitoneal injection of amygdalin (15 mg x kg(-1) x day(-1)). The rats were sacrificed 7, 14 and 28 days after bleomycin administration. Polarized light microscopy and Image-Pro Plus detected I and III collagen expressed in Paraffin-embedded lung sections stained with Sirius red. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) with weak cationic proteinchip (CM10) detected differentially expressed proteins in the pooled serum samples of all groups.</p><p><b>RESULTS</b>Consistent fibrotic responses were found in all bleomycin and amygdalin-tread groups. On the 7th, 14th and 28th day after bleomycin or saline instillation, four differentially expressed proteins were detected in the pooled serum of all groups rats, consisting of 4 proteins with mass/charge ratio of 3530.7, 7043.5, 8332.6 and 9068.0, respectively. Compared with control groups, protein peaks intensity ratio with mass/charge ratio of 3530.7 on 7, 28 d and 7043.5, 8332.6 and 9068.0 on 7, 14 and 28 d was > 2 in bleomycin-treated groups. Compared with amygdalin-treated groups, protein peaks intensity with mass/charge ratio of 3530.7 at 7, 14, 28 d had no change almost, but protein peaks intensity ratio with mass/charge ratio of 7043.5 at 7 d, 8332.6 on 28 d and 9068.0 on 14 d was > 2 in bleomycin-tread groups. All the four protein peaks intensity had no change almost at other point.</p><p><b>CONCLUSION</b>Amygdalin may reduce the bleomycin-induced increase of differentially expressed protein peak intensities in rat serum.</p>

Expression of FasL and apoptosis in pulmonary tissue of rats exposed to silica at different time / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the change of the expression of the FasL receptor and apoptosis in the pathology of silicosis of the rats exposed to silica and their roles.</p><p><b>METHODS</b>Ninety-six wistar rats were randomizedly divided into the control group and the experimental group. The silicotic animal model was established by the direct tracheal instillation of silica into rat lungs surgically. The control rats underwent directly tracheal instillation of saline into lungs surgically. Eight rats from each group were sacrificed at different days. The expression of FasL receptor in the tissue of the model rats was detected by tissuechip microarray and immunohistochemistry and the cell apoptosis induced by silica was determined by TdT-mediated dUTP nick end-labeling method. The integral optical density of positive cells were quantitatively analyzed using Image-Pro Plus Version 4.5 for windows.</p><p><b>RESULTS</b>The expression of FasL in the lung tissue of the model rats on the 7th, the 14th, the 21st, and the 28th day was significantly higher than that in the control group (P < 0.05), and peaked at the 14th day after exposure to silica. Apoptotic cells in the lung tissue of the model rats on the 1st, the 3rd, the 7th, the 14th, the 21st, and the 28th day were significantly more than those in the control group, and peaked at the 7th and the 14th day after exposure to silica.</p><p><b>CONCLUSION</b>Silica can lead to apoptosis in lung tissues. FasL is expressed in all kinds of cells in the pulmonary tissues of the rats exposed to silica and leads to apoptosis. From the 7th day to 14th day, inflammatory cells dominate in apoptotic cells.</p>

Effects of taurine on type I and III collagen expression in rats lung exposed to silica / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of taurine in diet on the expression of type I and III collagen and collagen ratio at different time points in rats lung by image process technology.</p><p><b>METHODS</b>Wistar rats were randomly divided into three groups: the saline instilled with a control diet (the saline treated group); silica instilled with a control diet (the silica treated group); and silica instilled with a diet containing 2.5% taurine (the taurine treated group). Animal models were established by the direct tracheal instillation of silica into rat lungs exposed surgically. The taurine concentration of serum was analyzed by means of HPLC. Paraffin embedded lung sections were stained with Sirius red. Polarization microscopy and Image Pro Plus Version 4.5 for windows were used for detecting type I and III collagen.</p><p><b>RESULTS</b>The concentration of taurine in serum of the taurine treated group was significantly elevated compared to the saline treated and silica treated group (P < 0.05 or P < 0.01). Sirius red polarization microscopy showed that type I and III collagen positive area percentage were elevated in the silica treated rats compared with the saline treated group. On the 7th, 14th, 21st, 28th day after silica instillation type I collagen positive area percentage was increased by 3.84, 3.77, 3.73, 9.83 respectively (P < 0.01), and type III collagen positive area percentage were elevated by a little in the silica treated rats compared with saline treated group. The taurine treatment significantly decreased elevation of silica type I collagen positive area percentage of lung by 2.39, 1.62, 7.13 at the 7th, 21st, 28th day respectively (P < 0.05 or P < 0.01), and type III collagen positive area percentage of lung by 2.62 at the 28th day (P < 0.05) compared with the silica treated group. The ratio of type I to III collagen was increased from the 7th day to 28th day after silica instillation, and reached 1.87 at the 28th day with the maximal ratio in the silica-treated group.</p><p><b>CONCLUSION</b>Treatment with taurine can effectively attenuate type I and III collagen expression in the rat lung induced by silica particles at different time points in our study.</p>