Deep learning for predicting the risk of immune checkpoint inhibitor-related pneumonitis in lung cancer.

AIM: To develop and validate a nomogram model that combines computed tomography (CT)-based radiological factors extracted from deep-learning and clinical factors for the early predictions of immune checkpoint inhibitor-related pneumonitis (ICI-P). MATERIALS AND METHODS: Forty ICI-P patients and 101 patients without ICI-P were divided randomly into the training (n=113) and test (n=28) sets. The convolution neural network (CNN) algorithm was used to extract the CT-based radiological features of predictable ICI-P and calculated the CT score of each patient. A nomogram model to predict the risk of ICI-P was developed by logistic regression. RESULTS: CT score was calculated from five radiological features extracted by the residual neural network-50-V2 with feature pyramid networks. Four predictors of ICI-P in the nomogram model included a clinical feature (pre-existing lung diseases), two serum markers (absolute lymphocyte count and lactate dehydrogenase), and a CT score. The area under curve of the nomogram model in the training (0.910 versus 0.871 versus 0.778) and test (0.900 versus 0.856 versus 0.869) sets was better than the radiological and clinical models. The nomogram model showed good consistency and better clinical practicability. CONCLUSION: The nomogram model that combined CT-based radiological factors and clinical factors can be used as a new non-invasive tool for the early prediction of ICI-P in lung cancer patients after immunotherapy with low cost and low manual input.

[Comparison between photodynamic therapy and interventional esophageal stent implantation in dysphagia caused by advanced esophageal cancer].

Objective: To compare the safety and efficacy of photodynamic therapy (PDT) and esophageal stent implantation in improving dysphagia caused by malignant obstruction of middle and advanced esophageal cancer. Methods: A total of 45 patients treated in the Affiliated Hospital of Qingdao University and Qingdao Huangdao District Central Hospital from January 2017 to January 2018 were retrospectively analyzed, of which 34 cases were males and 11 cases were females, 29 cases with the age beyond 60 years old, 41 cases were squamous carcinoma, 4 were adenocarcinoma. PDT was applied to 20 patients and 25 patients received esophageal carotid stenting implantation. There was no significant difference in gender, age, pathological type, location and stage between the two groups. Before treatment, 3 days, 1 month and 3 months after treatment, dysphagia was compared according to Stooler grading criteria, and also the time that patients experienced dysphagia again post treatment. Results: There were no statistical differences between the two groups in dysphagia grade change in 3 days, 1 month and 3 months after treatment (all P>0.05), The stent groups showed advantages towards the PDT group 3 days after treatment in patients with Stooler grading 0 (40%(10/25) vs 0(0/20), P<0.05). No significant differences were found between two groups with Stooler grading 0 (P>0.05) in 1 month and 3 months after treatment. Obstruction symptoms occurred earlier in the stent group compared with the PDT group (P<0.05). Conclusion: Esophageal stent can relieve the symptoms of dysphagia immediately after the implantation, while photodynamic therapy can also prolong the time of esophageal re-obstruction in addition to the immediate effect, with proved safety and efficacy in the treatment of middle and advanced esophageal cancer.

Decrease of FGF19 contributes to the increase of fasting glucose in human in an insulin-independent manner.

PURPOSE: The ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner. Here, we analyzed the association of FGF19 with glucose effectiveness (GE, the insulin-independent glucose regulation), as well as hepatic glucose production (HGP) in Chinese subjects. METHODS: GE was measured by frequently sampled intravenous glucose tolerance test (FSIVGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance (I-IGT), and isolated-impaired fasting glucose (I-IFG) subjects. The oral glucose tolerance test-derived surrogate of GE (oGE) was determined in NGT, I-IFG, combined glucose intolerance (CGI), and type 2 diabetes (T2DM) subjects. HGP was assessed by labeled ([3-3H]-glucose) hyperinsulinemic-euglycemic clamp in NGT subjects. Insulin secretion and sensitivity were calculated by the hyperglycemic and hyperinsulinemic-euglycemic clamps in a subgroup of NGT, I-IGT, and I-IFG subjects. Serum FGF19 levels were determined by ELISA. RESULTS: FGF19 positively correlated with GE (r = 0.29, P = 0.004) as determined by FSIVGTT. The result was further confirmed by oGE (r = 0.261, P < 0.001). FGF19 was negatively associated with FPG (r = - 0.228, P = 0.025), but the association no longer existed after adjusting for GE (r = - 0.177, P = 0.086). FGF19 was negatively associated with basal HGP (r = - 0.697, P = 0.006). However, the correlation between FGF19 and insulin secretion and sensitivity were not found. CONCLUSIONS: FGF19 levels are associated positively with GE and negatively with HGP. The increase of FPG in human is at least partially due to the decrease of FGF19 in an insulin-independent manner.

[Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space].

OBJECTIVE: To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS). METHODS: In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 µL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups. RESULTS: For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492). CONCLUSION: Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.

[Dynamic visual analysis of neutrophils chemotaxis in peritoneal cavity of schizophrenic model in mice].

OBJECTIVE: To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system. METHODS: In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis. RESULTS: The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×104/mL,(0.05±0.02)×104/mL,(0.32±0.01)×104/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) µm/s,(0.12±0.01) µm/s,(0.14±0.01) µm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) µm,(134.61±0.01) µm,(156.19±0.01) µm respectively(P<0.05). CONCLUSION: Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.

[A study of population pharmacokinetics of linezolid in Chinese].

Objective: To study the population pharmacokinetic (PPK) profiles of linezolid in Chinese healthy volunteers and infected patients. Methods: Linezolid 600 mg was administered to 31 Chinese healthy volunteers with a single dose and to 57 infected patients every 12 h for at least 5 doses. High performance liquid chromatography was applied to determine the plasma concentration of linezolid. Nonlinear mixed-effects modeling method was applied to analyze the PPK profiles. Results: For healthy volunteers with single dose of linezolid, 2-compartment with linear elimination model was the most appropriate structural pharmacokinetic model. The population typical value of apparent volume of central compartment was 26.99 L, volume of peripheral compartment was 22.22 L, apparent clearance of central compartment was 7.99 L/h, and clearance of peripheral compartment was 101.28 L/h. For each 1 kg deviation of weight from the mean value, 0.62 L of volume of peripheral compartment was correlated. For Chinese infected patients with multiple doses of linezolid, 1-compartment with linear elimination model was the most appropriate structural pharmacokinetic model. The population typical value of apparent volume was 38.85 L, and apparent clearance was 4.70 L/h. For each 1 kg deviation of weight from the mean value, 0.79 L of volume, as well as 0.04 L/h of clearance were correlated. For each 1 year deviation of age from the mean value, -0.045 L/h of clearance was correlated. Conclusions: The pharmacokinetic profiles of linezolid in Chinese simulate a 2-compartment with linear elimination model when single dose is administrated, and the weight is linearly positive-correlated to volume. While a 1-compartment with linear elimination model is appropriate when multiple doses are administrated, and the weight is linearly positive-correlated to volume and clearance, but the age is linearly negative-correlated to clearance.

Molecular identification and quantification of lactic acid bacteria in traditional fermented dairy foods of Russia.

Russian traditional fermented dairy foods have been consumed for thousands of years. However, little research has focused on exploiting lactic acid bacteria (LAB) resources and analyzing the LAB composition of Russian traditional fermented dairy foods. In the present study, we cultured LAB isolated from fermented mare and cow milks, sour cream, and cheese collected from Kalmykiya, Buryats, and Tuva regions of Russia. Seven lactobacillus species and the Bifidobacterium genus were quantified by quantitative PCR. The LAB counts in these samples ranged from 3.18 to 9.77 log cfu/mL (or per gram). In total, 599 LAB strains were obtained from these samples using de Man, Rogosa, and Sharpe agar and M17 agar. The identified LAB belonged to 7 genera and 30 species by 16S rRNA and murE gene sequencing and multiplex PCR assay. The predominant LAB isolates were Lactobacillus helveticus (176 strains) and Lactobacillus plantarum (63 strains), which represented 39.9% of all isolates. The quantitative PCR results revealed that counts of 7 lactobacilli species and Bifidobacterium spp. of 30 fermented cow milk samples ranged from 1.19±0.34 (Lactobacillus helveticus in Tuva) to 8.09±0.71 (Lactobacillus acidophilus in Kalmykiya) log cfu/mL of fermented cow milk (mean ± standard error). The numbers of Bifidobacterium spp., Lb. plantarum, Lb. helveticus, and Lb. acidophilus revealed no significant difference between the 3 regions; nevertheless, Lactobacillus paracasei, Lactobacillus fermentum, Lactobacillus sakei, and Lactobacillus delbrueckii ssp. bulgaricus exhibited different degrees of variation across 3 regions. The results demonstrate that traditional fermented dairy products from different regions of Russia have complex compositions of LAB species. The diversity of LAB might be related to the type of fermented dairy product, geographical origin, and manufacturing process.

A clinical study of pingyangmycin sclerotherapy for venous malformation: an evaluation of 281 consecutive patients.

WHAT IS KNOWN AND OBJECTIVE: In China, lidocaine together with 2 mg/mL of pingyangmycin (PYM, also known as bleomycin A5) is recommended for the treatment of venous malformations (VMs). The purpose of this study was to investigate whether lidocaine has a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Additionally, this study aimed to evaluate the outcomes of sclerotherapy for VMs using an intralesional injection of a low concentration of PYM (0·5 mg/mL). METHODS: A total of 281 patients with VMs were treated with 0·5 or 2 mg/mL of PYM with or without lidocaine and dexamethasone (DEX). All of the patients received a direct intralesional injection at a rate of 1 mL/min, and the volume of the solution varied from 1·5 to 6·0 mL per injection. RESULTS AND DISCUSSION: No significant differences were observed in the clinical outcomes between the PYM and PYM + lidocaine treatment groups (P > 0·05). The clinical outcomes were similar between the groups that were treated with 0·5 and 2 mg/mL of PYM, but the swelling and pain in the patients who were treated with 0·5 mg/mL of PYM were less severe compared with the patients who were treated with 2 mg/mL of PYM. A total of 29 patients with VM lesions on the glans penis were treated with 0·5 mg/mL of PYM + 0·5% lidocaine. Of these patients, 26 were cured, whereas three experienced a marked improvement. WHAT IS NEW AND CONCLUSION: Lidocaine does not have a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Sclerotherapy with a low concentration of PYM (0·5 mg/mL) combined with lidocaine and DEX is a safe and effective therapy for small superficial VMs of critical organs, such as the lips and the glans penis.

Plasmodium vivax: C-terminal diversity in the blood stage SERA genes from Indian field isolates.

The burden of Plasmodium vivax malaria is huge in India, affecting a large population annually. Recent reports of P. vivax contributing to severe illness and death, makes vaccine research on P. vivax malaria, a high priority. Extent of sequence variation in antigen coding genes is known to be a major hurdle in vaccine initiatives against malaria. Serine repeat antigens of Plasmodium are promising asexual blood stage vaccine candidates against malaria and have been implicated to have a key role in merozoite invasion and egress. Among the P. vivax SERA proteins, SERA4 and SERA5 are the major transcribed members in erythrocytic stages, making them encouraging candidates to be explored for their polymorphism and vaccine potential. Earlier reports suggest that diversity in these PvSERA antigens is localized to the C-terminal region of the proteins. Hence, genetic diversity study of this region seems prudent. Moreover, as there are no reports available from India, the present study aims to investigate the polymorphism in the C-terminal region of two highly transcribed members PvSERA4 and PvSERA5 in Indian field isolates. Our result of PvSERA5 demonstrates extensive genetic diversity, with major deletions, insertions and SNPs and signifies the gene to be under positive selection. On the other hand, high sequence conservation was seen in the PvSERA4 C-terminal region in Indian field isolates which was contrasting to earlier report from Thailand where they have shown diversity. Research data showcased in this study will greatly aid in gaining better understanding of antigenic variations, immune mediated selection mechanisms and the functional significance of these two vivax proteins. This study also makes a striking contribution towards understanding the antigenic repertoire of PvSERA genes in Indian isolates.

[Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears].

Objective: To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism. Methods: Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor ß1 (TGF-ß1) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-ß1 in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis. Results: On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-ß1 and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-ß1 and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-ß1 in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05). Conclusions: Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-ß1 and α-SMA in scar tissue.

Improving the system stability of a digital Shack-Hartmann wavefront sensor with a special lenslet array.

There has been very limited study on the stability of a Shack-Hartmann wavefront sensor (SHWS) since its emergence in the early 1970s. In this paper, through experimental study of the system stability of a digital SHWS, a special lenslet array with long focal range is designed and implemented with a spatial light modulator to improve the system performance. Diffractive lenses with long focal length range can provide pseudo-nondiffracting beams and a long range of focusing plane. The performance and effect of the modified SHWS with this lenslet array are investigated, and the experimental results show that the system stability and measurement repeatability are not sensitive to the sensing distance and stay at an acceptable level.

Asymmetrical optical lenslet array realized by spatial light modulator for measuring toroidal surfaces.

The Shack-Hartmann wavefront sensor (SHWS) recently has been extensively researched for optical surface metrology due to its extendable dynamic range compared with interferometry technique. In this paper, we proposed to use a digital SHWS to measure toroidal surfaces, which are widely used in many optical systems due to their different symmetries and curvatures in the X and Y directions. For what is believed to be the first time, an asymmetrical optical lenslet array implemented by a spatial light modulator was presented to tackle the measurement challenge. This unconventional design approach has a great advantage to provide different optical powers in the X and Y directions so that focusing spots can be formed and captured on the detector plane for accurate centroid finding and precise wavefront evaluation for 3D shape reconstruction of the toroidal surface. A digital SHWS system with this extraordinary microlens array was built to verify the design concept, and the experimental results were presented and analyzed.

MRFAP1 plays a protective role in neddylation inhibitor MLN4924-mediated gastric cancer cell death.

OBJECTIVE: MLN4924 is a second-generation small molecule inhibitor with anti-cancer activity that inhibits neddylation activation enzyme (NAE), subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs). Mof4 family associated protein 1 (MRFAP1) is a highly conserved, short half-life protein and one of the most up-regulated proteins in response to MLN4924 treatment. MRFAP1 has been identified as a novel cell cycle-related protein and a regulatory component monitoring and preventing genomic instability. However, whether MRFAP1 plays a role in MLN4924-mediated cancer cell death remains elusive. PATIENTS AND METHODS: The expression of MRFAP1 in gastric cancer clinic samples was detected by Real-time PCR and Western blot. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system was used to knockout MRFAP1 gene in both AGS and SGC-7901 cells. The proliferation of GC cells was measured by CCK8 assay. The cell cycle distribution of GC cells was determined by fluorescence-activated cell sorting (FACS) assay. Co-immunoprecipitation assay was used to determine the interaction between MRFAP1 and P27. RESULTS: MRFAP1 was downregulated in clinic gastric cancer samples at post-translational level. Overexpression of MRFAP1 decreased gastric cancer cells proliferation. CRISPR-mediated knockout of MRFAP1 increased the cytotoxicity of MLN4924 by augmenting MLN4924-induced G2/M arrest and apoptosis against gastric cancer cells. At the molecular level, we found that MLN4924 induced the interaction between P27 and MRFAP1, the latter associated with P27, which was further stabilized in response to MLN4924 treatment. CONCLUSIONS: We showed a protective role of MRFAP1 in gastric cancer cells with MLN4924 treatment and suggested the potential possibility to combine MLN4924 with MRFAP1 inhibition to treat gastric cancer.

Propranolol inhibits the proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms.

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.

An epidemic of poliomyelitis in southern Kerala.

An epidemic of poliomyelitis was recognized in May 1987 when there was a sharp increase in the number of children with acute paralytic poliomyelitis admitted to the SAT Hospital in Trivandrum in Kerala State. From May through September, 392 cases were admitted; the total admitted cases in 1987 were 458 in contrast to 119 in 1986. Evidence for type 1 poliovirus infection was found in 33 (85%) of the 39 children in whom virological investigations were done during the epidemic. In addition, evidence for poliovirus type 3 infection was found in four children. Data on the immunization status was available on 231 affected children in the epidemic; 175 (76%) had not received oral polio vaccine (OPV); 55 (24%) had received one or two doses and only one child had received three doses. Thus, lack of immunization was a major risk factor for disease. The estimated vaccine coverage with three doses of OPV in Kerala, based on the quantity of vaccine distributed during the years 1985, 1986 and 1987 were 94%, 100% and 91%, respectively. This outbreak occurred in spite of high vaccine coverage, and it illustrates the need for even higher coverage rates; the usefulness of hospitals as sentinel surveillance centres; the need for decentralized vaccine coverage data in order to prevent build-up of unimmunized susceptible children in any region; and the urgent need of a mechanism to respond to an epidemic quickly, with immunization, in order to curtail it.

Effect of coumarins on mitochondrial function I. Uncoupling of oxidative phosphorlation.

8-Acetyl-5,7-diemthoxy-4-phenylcoumarin at concentrations 0.03 to 0.3 mM uncoupled oxidative phosphorylation, in vitro, in rat liver mitochondria. Preincubation of mitochondria with the compound enhanced this effct. Similar uncoupling was observed with 5,7-dihydroxy-4phenylcoumarin; 7-acetonyloxycoumarin; 6,7-dimethyl-4-phenylcoumarin and 4-phenyldaphentin also. All these compounds stimulated mitochondrial ATPase activity three- to eight-fold. However, coumarin, the paretn substance of all these compounds had no effect on oxidative phosphorylation in mitochondria.

Effect of aflatoxins on oxidative phosphorylation by rat liver mitochondria.

The in vitro effect of aflatoxins M1, B1 and G1 on oxidative phosphorylation by rat liver mitochondria with succinate as substrate has been studied. All these toxins inhibit the electron transport chain at a 1-10-4 M concentration and the site of inhibition is between cytochrome b and cytochrome c or c1. Aflatoxin M1 (AFM1) uncouples oxidative phosphorylation at a concentration of 1-10-6 M and reduces the ADP:O ratio, whereas aflatoxin B1 (AFB1) at 1-10-6 M concentration uncouples oxidative phosphorulation but does not affect the ADP:O ratio. At a concentration of 1-10-5 M, AFB1 also decreases the ADP:O ratio along with the uncoupling of oxidative phosphorylation. Aflatoxin G1 (AFG1) acts as an uncoupler at a relatively higher concentration of 1-10-4 M. Preincubation of mitochondria with these aflatoxins resulted in inhibition of respiration and uncoupling of rat liver mitochondria.

Structure-activity relationships for rat and mouse LD50 of miscellaneous alcohols.

Structure-activity relationships between acute toxicities of 95 alcohols to rat and mouse (oral LD50) and four special sub-structure factors, hydroxyl number, carbon atom number were examined by means of expert system method. The results showed that the expert system based QSAR model was excellent for classification for miscellaneous alcohols (only 9 of them were wrong classified). It was also used to predict the toxicity of other 25 alcohols, and the false prediction rate was only 12%.

Effect of vitamin E on lipid components of atherogenic rats.

Rats were made atherogenic by feeding a synthetic diet containing high fat (20%) and cholesterol (2%) for two, three or four weeks. For alpha-tocopherol acetate supplementation studies, the rats on atherogenic diet for two weeks received alpha-tocopherol acetate 5 mg or 20 mg/100 g body weight once daily, orally for two weeks along with the atherogenic diet. Atherogenic diet fed rats showed elevated plasma cholesterol, hepatic total lipids, triglycerides and cholesterol and the increase in the constituents paralleled the period of feeding the diet. Administration of alpha-tocopherol acetate lowered the plasma cholesterol and hepatic lipid components in a dose-dependent manner. Supplementation with alpha-tocopherol acetate reduced the elevated osmotic fragility of erythrocytes from atherogenic diet fed rats to that of control levels. Thus alpha-tocopherol acetate administration to experimental atherogenic rats could normalize the altered lipid profile of atherogenesis and thereby reduce the risk for infarction.