CT imaging features of lung ground-glass nodule patients with upgraded intraoperative frozen pathology.

PURPOSE: Intraoperative frozen section pathology (FS) is widely used to guide surgical strategies while the accuracy is relatively low. Underestimating the pathological condition may result in inadequate surgical margins. This study aims to identify CT imaging features related to upgraded FS and develop a predictive model. METHODS: Collected data from 860 patients who underwent lung surgery from January to December 2019. We analyzed the consistency rate of FS and categorized the patients into three groups: Group 1 (n = 360) had both FS and Formalin-fixed Paraffin-embedded section (FP) as non-invasive adenocarcinoma (IAC); Group 2 (n = 128) had FS as non-IAC but FP as IAC; Group 3 (n = 372) had both FS and FP as IAC. Clinical baseline characteristics were compared and propensity score adjustment was used to mitigate the effects of these characteristics. Univariate analyses identified imaging features with inter-group differences. A multivariate analysis was conducted to screen independent risk factors for FS upgrade, after which a logistic regression prediction model was established and a receiver operating characteristic (ROC) curve was plotted. RESULTS: The consistency rate of FS with FP was 84.19%. 26.67% of the patients with non-IAC FS diagnosis were upgraded to IAC. The predictive model's Area Under Curve (AUC) is 0.785. Consolidation tumor ratio (CTR) ≤ 0.5 and smaller nodule diameter are associated with the underestimation of IAC in FS. CONCLUSION: CT imaging has the capacity to effectively detect patients at risk of upstaging during FS.

Balancing the Components of Biomass and the Reactivity of Pyrolysis Gas: Biomass-Assisted Recycling of Spent LiCoO2 Batteries.

Waste biomass is one of the promising feedstocks to supply syngas that can be used as fuels, chemicals, reductants, etc. However, the relationship between the component of biomass and the constituent of pyrolysis gas remains unclear. Here, we study the pyrolysis behaviors of various biomasses and reveal the relationship between the biomass components and gas compositions. Further, different pyrolysis gases are applied for the reduction of spent lithium cobalt oxide (LiCoO2) below 500 °C. The pyrolysis gas with a higher concentration of CO has a higher reductivity to convert LiCoO2 to CoO and Li2CO3 with a conversion rate close to 100% in 1 h at 500 °C. The biomass rich in cellulose and with a lower content of lignin tends to produce pyrolysis gas with a high concentration of CO, which comes from the deliberate breakdown of carboxyl, carbonyl, ether, and ester linkages. Moreover, LiCoO2 exerts catalytic functions over the deoxygenation and enhancement of oxygenates and single-ring aromatics. Overall, this paper offers a tailored approach to regulating biomass pyrolysis gases, enabling highly efficient battery recycling and syngas production.

An insertion of transposon in DcNAP inverted its function in the ethylene pathway to delay petal senescence in carnation (Dianthus caryophyllus L.).

Petal senescence is the final stage of flower development. Transcriptional regulation plays key roles in this process. However, whether and how post-transcriptional regulation involved is still largely unknown. Here, we identified an ethylene-induced NAC family transcription factor DcNAP in carnation (Dianthus caryophyllus L.). One allele, DcNAP-dTdic1, has an insertion of a dTdic1 transposon in its second exon. The dTdic1 transposon disrupts the structure of DcNAP and causes alternative splicing, which transcribes multiple domain-deleted variants (DcNAP2 and others). Conversely, the wild type allele DcNAP transcribes DcNAP1 encoding an intact NAC domain. Silencing DcNAP1 delays and overexpressing DcNAP1 accelerates petal senescence in carnation, while silencing and overexpressing DcNAP2 have the opposite effects, respectively. Further, DcNAP2 could interact with DcNAP1 and interfere the binding and activation activity of DcNAP1 to the promoters of its downstream target ethylene biosynthesis genes DcACS1 and DcACO1. Lastly, ethylene signalling core transcriptional factor DcEIL3-1 can activate the expression of DcNAP1 and DcNAP2 in the same way by binding their promoters. In summary, we discovered a novel mechanism by which DcNAP regulates carnation petal senescence at the post-transcriptional level. It may also provide a useful strategy to manipulate the NAC domains of NAC transcription factors for crop genetic improvement.

[Comparison of Two-dimensional and Three-dimensional Features of Chest CT
 in the Diagnosis of Invasion of Pulmonary Ground Glass Nodules].

BACKGROUND: At present, more and more studies predict invasive adenocarcinoma (IAC) through three-dimensional features of pulmonary nodules, but few studies have confirmed that three-dimensional features have more advantages in diagnosing IAC than traditional two-dimensional features of pulmonary nodules. This study analyzed the differences of chest computed tomography (CT) features between IAC and minimally invasive adenocarcinoma (MIA) from three-dimensional and two-dimensional levels, and compared the ability of diagnosing IAC. The non-invasive adenocarcinoma group includes precursor glandular lesions (PGL) and minimally invasive adenocarcinoma (MIA). METHODS: The clinical data of 1,045 patients with ground glass opacity (GGO) from January to December 2019 were collected. Then the correlation between preoperative CT image characteristics and pathological results were analyzed retrospectively. The independent influencing factors for the identification of IAC were screened out according to two-dimensional and three-dimensional classification by multivariate Logistic regression and the cut-off point for the identification of IAC was found out through the receiver operating characteristic (ROC) curve. At last, the ability of diagnosing IAC was evaluated by Yoden index. RESULTS: The diameter of nodule, the diameter of solid component, the diameter of mediastinal window nodule in two-dimensional factors, and the volume of nodule, the volume of solid part and the average CT value in three-dimensional factors were independent risk factors for the diagnosis of IAC. These factors were arranged by Yoden index: solid partial volume (0.601)>nodule volume (0.536)>solid component diameter (0.525)>nodule diameter (0.518)>mediastinal window nodule diameter (0.488)>proportion of solid component volume (0.471)>1-tumor disappearance ratio (TDR) (0.468)>consolidation tumor ratio (CTR) (0.394)>average CT value (0.380). CONCLUSIONS: The CT features of three-dimensional are better than two-dimensional in the diagnosis of IAC, and the size of solid components is better than the overall size of nodules.

Diammonium glycyrrhizinate ameliorates portal hypertension by regulating portal macrophage oxidation and superoxide dismutase 3.

Portal hypertension (PHT) is a complication of liver diseases. Increased intrahepatic vascular resistance is attributed to reduced bioavailability of vasodilator substances. The macrophage activation and superoxide dismutase 3 (SOD3) involve in the pathogenesis of PHT. Diammonium glycyrrhizinate (DG) is the salt form of glycyrrhizin derived from Radix glycyrrhizae, exerting anti-oxidant activities and be beneficial for liver injury. Here, we aimed to investigate effects of DG on PHT and explore its underlying mechanisms on regulation of macrophages and SOD3. The carbon tetrachloride induced PHT rats received administration of liposome-encapsulated clodronate for hepatic macrophage depletion, or PBS liposomes for matched control. DG (25 mg/kg) or vehicle was gavaged. Portal pressure in vivo, and serum biomarkers of macrophage activation were measured. The nitric oxide (NO) and prostacyclin (PGI2) bioavailability was evaluated in the isolated portal perfused rat livers. Liver tissues were collected to evaluate cirrhosis, macrophage oxidation, and SOD3 activity. Depletion of hepatic macrophages decreased portal pressure, increased bioavailability of NO and PGI2, and restored SOD3 activity. DG effectively decreased portal pressure, relieved cirrhosis, inhibited macrophage activation. DG increased bioavailability of NO and PGI2 to relax portal veins. DG relieved portal macrophage oxidation through decreasing nicotinamide adenine dinucleotide phosphate oxidase 2 and inducible NO synthase expressions, elevated SOD3 activities and increased SOD3 expressions at portal triads. These findings indicated that DG restored SOD3 activity, against portal macrophage oxidation, protected bioavailability of NO and PGI2, thereby reduced portal pressure. It suggested a potential use of DG for PHT treatment.

A novel model of dermatomyositis induced by membrane antigen and calciphylaxis in rats.

Dermatomyositis (DM) is a severe autoimmune disease of the connective tissue characterized by inflammatory and degenerative changes in the skin and muscle. However, the lack of experimental models of DM represents a challenge for the development of effective drugs. The aim of the present study was to establish a pharmacodynamic rat model of DM that would recapitulate the clinical manifestation seen in patients. The DM model was established using membrane antigen-induced autoimmune injury, followed by toxin-induced subcutaneous calciphylaxis. The rats were divided into five groups and were subcutaneously injected with membrane antigen. Of these, four antigen-immunized groups then received dihydrotestosterone (DHT), iron-dextrin (Fe-Dex), polymyxin (PMX) either individually or in combination to induce cutaneous calciphylaxis. The clinical manifestation score, ratio of infiltrated lymphocytes, ratio of arteriole calcified nodules in skeletal muscles, serum antibody levels [anti-histidyl tRNA synthetase (Jo-1) and anti-melanoma differentiation-associated protein 5 (MDA5)] and serum cytokine levels [tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] were then detected. The results demonstrated that all five autoimmune groups displayed local cutaneous swelling and weakness, increased serum antibody and cytokine levels, and T lymphocyte infiltration in perimysial and perivascular sites. Moreover, pathological changes indicative of calciphylaxis were observed in the PMX and DHT + Fe-Dex + PMX. Among all groups, the rats in the PMX and DHT + Fe-Dex + PMX displayed characteristics most closely resembling those of DM pathogenesis in patients. In conclusion, membrane antigen immunization combined with toxin-induced calciphylaxis can be used as a DM model in rats. This model may be used for the development of effective drugs for DM treatment.

[Relationship between EGFR, ALK Gene Mutation and Imaging 
and Pathological Features in Invasive Lung Adenocarcinoma].

BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS: The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.

[Research Progress in 3D-reconstruction Based Imaging Analysis 
in Partial Solid Pulmonary Nodule].

The incidence and mortality of lung cancer rank first among all malignant tumors in China. With the popularization of high resolution computed tomography (CT) in clinic, chest CT has become an important means of clinical screening for early lung cancer and reducing the mortality of lung cancer. Imaging findings of early lung adenocarcinoma often show partial solid nodules with ground glass components. With the development of imaging, the relationship between the imaging features of some solid nodules and their prognosis has attracted more and more attention. At the same time, with the development of 3D-reconstruction technology, clinicians can improve the accuracy of diagnosis and treatment of such nodules.This article focuses on the traditional imaging analysis of partial solid nodules and the imaging analysis based on 3D reconstruction, and systematically expounds the advantages and disadvantages of both.
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[Effect of traditional Chinese medicine massage on the rehabilitation of spinal function in scoliosis patients undergoing 3D printing orthopedic surgery].

OBJECTIVE: To explore the effect of Chinese massage on the rehabilitation of scoliosis patients undergoing 3D printing orthopedics. METHODS: A retrospective selection of 262 patients with adolescent idiopathic scoliosis(AIS) who underwent 3D printing technology orthopedics admitted to the Department of Orthopedics in our hospital from January 2013 to January 2019 were selected for clinical research. According to the rehabilitation treatment methods adopted by the patients after the operation, the patients were divided into control group and observation group, there were 131 cases in each group. The observation group was treated with traditional Chinese acupuncture and massage after operation, and the control group was treated with conventional rehabilitation. The torso rotation angle and the maximum Cobb angle before and after intervention were measured and compared between two groups, Oswestry Disability Index(ODI) was used for functional evaluation, and the visual analogue scale(VAS) was used to evaluate the changes in pain before and after rehabilitation intervention. RESULTS: After the intervention, the trunk rotation angle and maximum Cobb angle of the observation group were significantly better than those of the control group, the VAS score of the observation group was significantly lower than that of the control group, ODI in the observation group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). CONCLUSION: After scoliosis patients undergo preoperative 3D printing correction, the scientific and reasonable implementation of TCM acupuncture and massage can effectively improve the patient's vertebral rotation angle, maximum Cobb angle, and improve the patient's spinal function.

Computed tomography image fusion, Coaxial guidewire technique, Fast intraprocedural cortisol testing technique improves success rate and decreases radiation exposure, procedure time, and contrast use for adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) is recommended for discriminating patients with unilateral primary aldosteronism from bilateral disease. However, it is a technically demanding procedure that is markedly underused. We developed a computed tomography image fusion, coaxial guidewire technique, fast intraprocedural cortisol testing (CCF) technique to improve AVS success rate, which combines CT image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing. OBJECTIVE: To evaluate the effectiveness and safety of the AVS--CCF technique. METHODS: We retrospectively evaluated 105 patients who undervent AVS from June 2016 to October 2020. There were 51 patients in the AVS--CCF group and 54 patients in the AVS group. We compared two groups with technical success rate, procedure time, radiation exposure, volume of contrast medium, and complications (adrenal vein rupture, dissection, infarction, or thrombosis; intraglandular or periadrenal hematoma; and contrast-induced nephropathy). RESULTS: The technical success rate was higher for AVS--CCF than for AVS without CCF (98 vs. 83.3% for bilateral adrenal veins, P = 0.016). AVS--CCF was associated with a shorter procedure time (63.6 ±â€Š24.6 vs. 94.8 ±â€Š40.8 min, P < 0.001), shorter fluoroscopy time (15.6 ±â€Š12.6 vs. 20.4 ±â€Š15.0 min, P = 0.043), and lower contrast medium volume (25.10 ±â€Š21.82 vs. 44.1 ±â€Š31.0 ml, P < 0.001). There were no significant differences between groups with respect to the time for cannulating the left or right adrenal vein or the peak skin radiation dose. Adrenal vein rupture occurred in 14 patients and intraglandular hematoma in 1 patient. CONCLUSION: The CCF technique during AVS not only contributed to improved technical success rates but also associated with decreased procedure time, radiation exposure, and contrast medium volume.

Impact of hyperlipidemia as a coexisting factor on the prognosis of idiopathic sudden sensorineural hearing loss: A propensity score matching analysis.

OBJECTIVE: To define the impact of hyperlipidemia as a coexisting factor on the prognosis of Idiopathic Sudden Sensorineural Hearing Loss (ISSHL), we prospectively analysed the Lipid-lowering therapy Group (LLTG) data compared with Control Group (CG) data to determine the effects of Lipid intervention on the prognosis of sudden hearing loss. DESIGN: A prospective, non-randomized study. SETTING: Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China. PARTICIPANTS: A total of 653 in-patient SSHL patients were enrolled between January 2014 to August 2018. MAIN OUTCOME MEASURES: From January 2014 to August 2018, 653 patients with ISSHL who also had hyperlipidemia as coexisting factor were identified. Patients enrolled in LLTG (n = 200) or CG (n = 453) were compared by a propensity score matching analysis (PSM, caliper = 0.01, n = 2) to balance pre-existing clinical characteristics. After matching, the effective rate of different hyperlipidemia types and different types of audiogram in both groups were performed by Cochran-Mantel-Haenszel test (CMH). RESULTS: After PSM, 440 patients were studied (146 in LLTG, 294 in CG), and the influence of interference factors was balanced, meanwhile, the final hearing level was better in LLTG than CG (P = .043), and hearing gain was higher in LLTG than CG (P = .006). Cure rate (32.9%), significant improvement rate (22.6%) and the total effective rate (76.0%) in LLTG were better than that in CG group (26.5%, 15.6% and 63.6%) after the Pearson chi-square test (P < .05). Analysis with the Cochran-Mantel-Haenszel test showed that the total effective rate was better in LLTG than CG respectively (P = .009) in each different hyperlipidemia types, and there were statistically significant differences in TG higher group (TG Group; P = .018). Moreover, the total effective rate was better in LLTG than CG (P = .006) for all patterns of audiogram, and there were statistically significant differences in flat audiogram (P = .043). CONCLUSIONS: Lipid-lowering therapy can improve the curative effect of sudden hearing loss patients combined with hyperlipidemia. There was a significant difference in the total effective rate of TG Group after lipid intervention, suggesting that there might be causal relationship between TG and sudden hearing loss. There was a significant difference in the total effective rate between flat audiogram, which may suggest flat hearing loss was more likely caused by vascular dysfunction.

Updated Oxford classification and the international study of kidney disease in children classification: application in predicting outcome of Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) shares many similarities with IgA nephropathy. We aimed to analyze the predictive value of the International Study of Kidney Disease in Children (ISKDC) classification and the updated Oxford classification for IgA nephropathy in HSPN patients. METHODS: Data of 275 HSPN patients (aged≥14 years) were retrieved, and all of them underwent a renal biopsy. We re-classified the biopsies according to the ISKDC classification and the updated Oxford classification to analyze their correlations with clinical features and renal outcomes. The renal endpoints were defined as ≥30% reduction in baseline estimated glomerular filtration rate (eGFR) in 2 years, doubling of serum creatinine (Scr) or end stage renal disease. RESULTS: During follow-up period of 56(30,86) months, 30(10.9%) patients reached renal endpoints. Segmental sclerosis was the only pathological feature independently associated with renal endpoints (HR 4.086, 95%CI 1.111-15.026, P = 0.034). Tubular atrophy/ interstitial fibrosis was associated with eGFR and Scr levels, and its correlation with renal endpoints was found by univariate analysis. Endocapillary hypercellularity was associated with 24 h urine protein and is of prognostic value in univariate analysis. Mesangial hypercellularity was not associated with clinical features or renal endpoints. Crescents were associated with 24 h urine protein, Scr and eGFR levels, but both ISKDC and updated Oxford classifications of crescents were not associated with renal endpoints by multivariate analysis. CONCLUSIONS: The updated Oxford classification can help in disease management and renal outcome prediction of HSPN.

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor.

Primary ovarian cancer is the main cause of gynecological cancer-associated mortality. However, the mechanism behind the spread of ovarian cancer requires elucidation. The present study aimed to investigate the effects of microRNA-126 (miR-126) on differentiation and invasion, and its mechanism in primary ovarian cancer. Ovarian cancer SKOV3 cells transfected with LV3-has-miR-126 mimics and LV3-has-miR-126 inhibitor were produced; it was revealedthatLV-miR-126 mimics could induce cell cycle arrest at G1 phase, suppress cell invasion through Matrigel-coated membranes and downregulate the expression of vascular endothelial growth factor (VEGF). Furthermore, LV-has-miR-126 inhibitor-transfected cells could increase the number of cells in S phase, induce cell invasion and upregulate the expression of VEGF. The present study, to the best of our knowledge, is the first to report that miR-126 may serve tumor suppressor roles by inducing G1 cell cycle arrest and suppressing invasion in ovarian cancer cells, at least in part by targeting VEGF expression.

The Crescentic Implication of Renal Outcomes in Proliferative Lupus Nephritis.

OBJECTIVE: To determine the association between crescents and renal outcomes, and the implications on therapeutic choices. METHODS: There were 231 patients with biopsy-proven proliferative lupus nephritis (PLN) who were divided into 4 groups: 59 patients were in the noncrescent group (NC); 59 patients exclusively with segmental crescents were in the segmental crescent group (SC); patients with circumferential crescents were categorized into 2 groups according to the crescentic ratio (C1 had 64 patients with ≤ 25%, and C2 had 49 patients with > 25%). Their baseline laboratory tests, histopathological manifestations, and outcomes were compared. RESULTS: Remission rates in NC, SC, C1, and C2 groups were 92.1%, 85.4%, 95.0%, and 76.1%, respectively. Fewer patients in the C2 group achieved complete remission than the other 3 groups. For longterm outcomes evaluated by serum creatinine (SCr) doubling or endstage renal disease (ESRD), the renal survival rate was lowest in the C2 group (p = 0.003). Including clinical and pathological variables in the Cox proportional hazard regression model separately, the multivariate analysis revealed that these were independent risk factors for SCr doubling or ESRD: baseline SCr (with every 1 mg/dl increase: HR = 1.834, 95% CI 1.465-2.296; p < 0.001), hemoglobin (with every 1 g/l increase: HR = 0.970, 95% CI 0.947-0.992; p = 0.009), the proportions of cellular crescents (with every 1% increase: HR = 1.040, 95% CI 1.015-1.066; p = 0.002) and fibrocellular crescents (with every 1% increase: HR = 1.085, 95% CI 1.013-1.163; p = 0.020), and severe renal tubular atrophy (HR = 5.348, 95% CI 1.278-22.373; p = 0.022). CONCLUSION: PLN with crescents > 25% had worse renal outcomes both in short and long terms. Proportions of cellular and fibrocellular crescents were independent risk factors for poor renal survival.

The expression of the Slit-Robo signal in the retina of diabetic rats and the vitreous or fibrovascular retinal membranes of patients with proliferative diabetic retinopathy.

PURPOSE: The Slit-Robo signal has an important role in vasculogenesis and angiogenesis. Our study examined the expression of Slit2 and its receptor, Robo1, in a rat model of streptozotocin-induced diabetes and in patients with proliferative diabetic retinopathy. METHODS: Diabetes was induced in male Sprague-Dawley rats via a single, intraperitoneal injection of streptozotocin. The rats were sacrificed 1, 3 or 6 months after the injection. The expression of Slit2 and Robo1 in retinal tissue was measured by real-time reverse transcription polymerase chain reaction (RT-PCR), and protein levels were measured by western blotting and immunohistochemistry. Recombinant N-Slit2 protein was used to study the effects of Slit2 on the expression of VEGF in vivo. The concentration of Slit2 protein in human eyes was measured by enzyme-linked immunosorbent assay in 27 eyes with proliferative diabetic retinopathy and 28 eyes in control group. The expression of Slit2, Robo1 and VEGF in the excised human fibrovascular membranes was examined by fluorescence immunostaining and semi-quantitative RT-PCR. RESULTS: The expression of Slit2 and Robo1 in the retina was altered after STZ injection. Recombinant N-Slit2 protein did not increase the retinal VEGF expression. Vitreous concentrations of Slit2 were significantly higher in the study group than in the control group. In the human fibrovascular membranes of the study group, the co-localization of VEGF with the markers for Slit2 and Robo1was observed. The expression of Slit2 mRNA, Robo1 mRNA, and VEGF mRNA was significantly higher in human fibrovascular proliferative diabetic retinopathy membranes than in the control membranes. CONCLUSIONS: The alteration of Slit2 and Robo1 expression in the retinas of diabetic rats and patients with proliferative diabetic retinopathy suggests a role for the Slit-Robo signal in the various stages diabetic retinopathy. Further studies should address the possible involvement of the Slit-Robo signal in the pathophysiological progress of diabetic retinopathy.

Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro.

Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Cells were treated with various concentrations of metformin and then evaluated with respect to viability, proliferation, adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆ψm), and the expression of anti- and pro-apoptotic proteins. Metformin caused apoptosis in a concentration- and time-dependent manner, and decreased cell viability and ATP production. Furthermore, metformin induced the generation of ROS and decreased the ∆ψm. Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. These results demonstrate that the apoptotic and cytotoxic effects of metformin on breast cancer cells are mediated by the intrinsic mitochondria-mediated apoptosis pathway.

[Correlations between the pathogenesis and prognosis of sudden sensorineural hearing loss and blood lipid].

OBJECTIVE: We aimed to determine whether blood lipid parameters were related to the severity and the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) patients. METHODS: A retrospective cohort study of 258 patients with ISSNHL from December 2013 to February 2015. The distribution characteristics of lipids [total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Non-high-density lipoprotein cholesterol (Non-HDL-C), et al] in different degree of deafness (mild, moderate, severe, and profound), hearing curve types (low frequency, high frequency, full range frequency, and completely deafness type) and prognosis of recovery (complete, partial, slight, and no recovery) were analyzed by IBM SPSS 22.0 ANOVA analysis, chi square test and multiple regression analysis. RESULTS: TG level in mild hearing loss group was significantly lower than that in severe and profound hearing loss group (P = 0.017 and P = 0.007). There were no correlation between curve types and lipid indexes (P > 0.05). Non-HDL-C level was elevated in no recovery and slight recovery groups (P = 0.026 and 0.021). TC levels in partial recovery group and no recovery group were significantly higher than that in the complete recovery group (P = 0.049 and 0.042), TG was higher in slight recovery group (P = 0.014). CONCLUSIONS: TG has significant correlation with the severity of hearing loss. There are negative correlations between hearing recovery and Non-HDL-C, TC and TG levels. Non-HDL-C, TC and TG might be a prognostic factor for treatment outcome in ISSNHL patients.

SRPX2 promotes cell migration and invasion via FAK dependent pathway in pancreatic cancer.

Sushi repeat-containing protein, X-linked 2, abbreviated as SRPX2, is a candidate downstream target protein for E2A-HLF and involved in disorders of language cortex and cognition. Recent studies have demonstrated that elevated SRPX2 exhibits crucial roles in gastric cancer, however, underlying clinical significance and biological function of SRPX2 in pancreatic ductal adenocarcinoma (PDAC), remains unclear. Data from Oncomine database showed that higher SRPX2 expression is more commonly observed in PDAC compared with normal pancreatic duct, similar results were also found in 12 matched PDAC tissue samples, 7 PDAC cell lines and a tissue microarray containing 81 PDAC specimens as demonstrated by real-time quantitative PCR and immunohistochemistry, respectively. Besides, higher SRPX2 expression was closely correlated with advanced TNM stage. Silencing of endogenous SRPX2 expression reduced abilities of cell migration and invasion of PDAC cells. Further studies revealed that SRPX2 expression in PDAC tissues significantly correlated with the phosphorylation levels of FAK, indicating that FAK dependent pathway may be account for the effect of SRPX2 on cell migration and invasion in PDAC. Collectively, this study reveals that frequently elevated SRPX2 contributes to cell migration and invasion in PDAC and SRPX2-related pathways might be a potential therapeutic target for PDAC.