Objective To summarize the research results at home and abroad of raltitrexed on the patients with advanced gastric cancer,and to evaluate the clinical efficacy and adverse reactions of raltitrexed. Methods Clinical controlled trials of evaluating effects of raltitrexed on the advanced gastric cancer were searched in PubMed,EMBase,Ovid,Springer,Wanfang database,VIP database and China Biology Medicine disc. Besides,references and conference abstracts were searched manually. Literature screening and data extraction were performed according to inclusion and exclusion criteria. Then Meta-analysis was performed using RevMan 4. 2. Results Forty-four studies were found and 5 clinical controlled trails including 338 patients were included in this analysis. The results of Meta-analysis showed that there was a significant beneficial effect of raltitrexed on objective effective rate for the patients with advanced gastric cancer(RR = 1. 55,95% CI:1. 21-1. 99,Z = 3. 44,P = 0. 00)compared with other treatments. The incidences of Ⅲ-Ⅳadverse reactions in raltit-rexed group such as neutropenia(RR = 1. 97,95% CI:0. 85-4. 56,Z = 1. 59,P = 0. 11),thrombocytopenia (RR = 1. 56,95% CI:0. 60-4. 07,Z = 0. 92,P = 0. 36),anemia(RR = 2. 43,95% CI:0. 61-9. 78,Z =1. 25,P = 0. 21),arthralgia(RR = 3. 20,95% CI:0. 73-13. 98,Z = 1. 55,P = 0. 12),elevated transaminase (RR = 1. 37,95% CI:0. 29-6. 48,Z = 0. 39,P = 0. 69)were higher than those in other group,with no statis-tical significance. However,the adverse reactions in raltitrexed group such as diarrhea(RR = 0. 18,95% CI:0. 03-1. 07,Z = 1. 88,P = 0. 06),nausea and vomiting(Z = 1. 79,RR = 0. 45,95% CI:0. 19-1. 08,P =0. 07),neurotoxicity(RR = 0. 07,95% CI:0. 01-0. 52,Z = 2. 59,P = 0. 01),hand-foot syndrome(RR =0. 26,95% CI:0. 04-1. 59,Z = 1. 46,P = 0. 14),alopecia(RR = 0. 57,95% CI:0. 13-2. 55,Z = 0. 73, P = 0. 46)were lower than those in other group. There were no statistical significances except neurotoxicity. Conclusion Compared with other treatments,raltitrexed-based chemotherapy has a beneficial effect on objec-tive effective rate and less adverse reactions for the patients with advanced gastric cancer,which is worthy of clinical use.

Background Proliferative vitreoretinopathy (PVR):no blood vessels,fibrous membrane cell proliferation occurs retinal surface.The development of specific mechanisms has not been completely clarified,but the retinal pigment epithelium(RPE) and platelet-derived growth factor(PDGF) for the past few years are the research hotspot.Objective To explore the effects of hypoxia on the production of PDGF-BB and proliferation in cultured human RPE (hRPE) cells.Methods In the experimental group,10,15,20,30,40 μmol/L CoCl2 were used to mimic hypoxia environment of hRPE cells,the control group did not add CoCl2 on cultured hRPE cells.By using reverse transcriptive PCR (RT-PCR) and enzyme linked immunosorbent assay(ELISA),the expression of PDGF-BB mRNA and protein was detected,and detected proliferation of hRPE cells by MTT.The cells were divided into 6 groups,different siRNAs were transfected into PDGF-BB siRNA1 group,PDGF-BB siRNA2 group,PDGF-BB siRNA3 group (because PDGF-BB has three different siRNAs,one of which is a valid siRNA),β-actin siRNA group,unrelated sequence siRNA group,only Lip2000 was plused in the blank control group.After transfection of 4-6 hours,except for blank control group,the other five groups were added to PDGF-BB mRNA and protein and its effect on the proliferation of hRPE cells obviously CoCl2 concentrations (15 μmol/L) simulated hypoxia environment of 24 hours,the detection of PDGF-BB mRNA and protein and hRPE cell proliferation rate.Results Neither PDGF-BB mRNA or protein was found in the blank control group.The production of PDGF-BB mRNA and protein in hRPE cells cultured by different concentrations were different,with significant differences among them (F=43.737,P＜0.01;F=54.612,P＜0.05),and the expressions of PDGF-BB mRNA and protein of 15 μmol/L CoCl2 group were more than other groups,with significant differences between the two groups (all at P＜0.05).MTT showed that PDGF-BB protein and hRPE cell proliferation rate in different concentions of CoCl2 groups were different,with significant differences among them(F=95.379,P＜0.01 ; F =63.375,P＜0.05),the expression of PDGF-BB protein was more and hRPE cell proliferation rate was higher in 15 μmol/L CoCl2group than other groups,with significant differences between the two groups (all at P＜0.05),postive correlation was found between PDGF-BB protein and hRPE cell proliferation rate (r =0.994,P＜0.05).The production of PDGF-BB mRNA and protein in the different siRNA transfected groups were different,with significant differences among them (F =156.330,125.650,both at P＜0.01),and the expressions of PDGF-BB mRNA and protein of PDGF-BB siRNA2 group were more than other groups,with significant differences between them(all at P＜0.05).MTT showed that PDGF-BB protein and hRPE cell proliferation rate in different siRNA transfectedgroups were different,with significant differences among them (F =73.131,98.564,both at P＜ 0.01).The expression of PDGF-BB protein was less and hRPE cell proliferation rate was lower in PDGF-BB siRNA2 group than other groups,with significant differences between them (all at P ＜ 0.05),postive correlation was found between PDGF-BB protein and hRPE cell proliferation rate (r =0.996,P＜0.05).Conclusions Proper hypoxia can induce the expression of PDGF-BB,PDGF-BB expression can significantly promote the proliferation of hRPE cells.In the transfection targeting PDGF-BB siRNA,PDGF-BB expression is suppressed,can effectively reduce the value of hRPE cell hyperplasia.

Hydroxychloroquine retinopathy is an ocular lesions that develops following long-term or excessive use of hydroxychloroquine. The early clinical presentation of this lesion is nonspecific and is often detected when severe central vision impairment occurs in late stage. It currently mainly includes hydroxychloroquine binding to melanin, inducing degeneration of the retinal pigment epithelium, increasing the pH of lysosomes in the retinal pigment epithelium and interfering with the visual cycle. In recent years, with the development of retinal imaging technology and the in-depth study of hydroxychloroquine retinopathy, characteristic fundus structural changes such as retinal and choroidal thickness and blood vessels may occur in the early stage. This not only provides an important basis for the early diagnosis of hydroxychloroquine retinopathy, but also provides important clues for investigating its pathogenesis. Clinicians' proficiency in relevant fundus changes and pathogenesis will facilitate early diagnosis and treatment, while also minimizing irreversible central vision impairment in patients.

OBJECTIVETo identify a HEK293 cell line containing stably-transfected H3R gene, and to screen the novel non-imidazole compounds with H3R antagonist activity.

METHODSThe expression of rat H3 receptor in cell line was detected by RT-PCR and Western blot. An elevation of intercellular cAMP concentration induced by forskolin was measured as the index for screening compounds with H3R antagonist activity.

RESULTSThe H3R-transfected HEK-293 cells stably expressed high level of rat H3 receptor mRNA and protein. Forskolin significantly increased intercellular cAMP concentration in the H3R-transfected HEK-293 cells. H3R agonist (R)-α-methylhistamine inhibited the forskolin-induced production of intercellular cAMP. H3R antagonist thioperamide and newly synthesized non-imidazole compounds XHA23 and XHA25 blocked (R)-α- methylhistamine reversal of forskolin-induced cAMP formation in a concentration-dependent manner, and the IC50 values were 3.62 μmol/L, 0.49 μmol/L, 0.14 μmol/L, respectively.

CONCLUSIONThe H3R-transfected HEK293 cells stably express high level of rat H3 receptor, and can be used for screening compounds with H3R antagonist activity. The non-imidazole compounds XHA23 and XHA25 may have H3R antagonist activity.

Animals ; Drug Evaluation, Preclinical ; HEK293 Cells ; Histamine H3 Antagonists ; Humans ; Rats ; Receptors, Histamine H3 ; genetics ; metabolism ; Transfection

OBJECTIVETo evaluate the effects of aminoguanidine on methylglyoxal-mediated oxygen-glucose deprivation (OGD) injury in the cultured human brain microvascular endothelial cells (HBMEC).

METHODSCultured HBMEC cells were pretreated with methylglyoxal before oxygen-glucose deprivation injury. Cell vitality was determined by MTT method, cell mortality was assessed by LDH release method, cell apoptosis was examined by Annexin V/PI formation method, and the advanced glycation end products (AGEs) were detected by Western-blot.

RESULTSMethylglyoxal induced HBMEC injury in a dose-dependent manner. At 2 mmol/L of methylglyoxal, the cell viability was 56.1% when methylglyoxal-pretreated cells exposed to oxygen-glucose deprivation, the cell inhibition rate was 90.0%. Aminoguanidine (1 mmol/L) inhibited methylglyoxal and OGD induced LDH release and Annexin V/PI formation. Furthermore, aminoguanidine (1 mmol/L) also decreased advanced glycation end products (AGEs) formation induced by methylglyoxal and oxygen-glucose deprivation.

CONCLUSIONAminoguanidine protected methylglyoxal mediated-oxygen-glucose deprivation injury in the cultured HBMEC, which may be associated with anti-glycation activity.

Apoptosis ; drug effects ; Cell Hypoxia ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Drug Antagonism ; Endothelial Cells ; drug effects ; metabolism ; pathology ; Endothelium, Vascular ; cytology ; Glycation End Products, Advanced ; metabolism ; Guanidines ; pharmacology ; Humans ; Pyruvaldehyde ; pharmacology

Objective To explore the value of CT quantitative analysis in differentiating lepidicGpredominant adenocarcinoma (LPA)from invasive nonGlepidicGpredominant adenocarcinoma (INV)manifested as subsolid nodules (SSN).Methods A total of patients with lung adenocarcinoma manifested as SSNs on CT images were divided into LPA group and INV group according to their pathological results.Total volume,solid volume,solid volume percentage,total mass,solid mass,solid mass percentage and threeGdimensional mean CT value of the nodules were calculated after segmenting pulmonary nodules by a 3DGCT segmentation software,meanwhile the oneGdimensional mean CT value and maximal diameter were manually measured.SPSS 22.0 software was used for statistical analysis. Results Solid volume (0.1 6 ±0.3 6 cm3 vs 1.2 6 ±2.1 7 cm3 ,P＜0.00 1),solid volume percentage (4.7 9 ±5.40% vs 2 6.3 3 ± 1 5.6 3%, P＜0.001),total mass (1 180.64±1 751.46 mg vs 2 386.59±3 224.54 mg,P＝0.010),solid mass (151.64±337.53 mg vs 1 257.34± 2 220.9 2 mg,P＜0.00 1 ),solid mass percentage (7.9 8 ± 8.5 8% vs 3 7.2 3 ± 1 8.83%,P＜0.00 1 ),threeGdimensional mean CT value (－492.26±71.21 HU vs －350.73±94.52 HU,P＜0.001 )and oneGdimensional mean CT value (－472.29 ± 1 12.46 HU vs －282.02 ± 1 5 9.13 HU,P＜0.001)in LPA group were found significantly lower than those in INV group.There were no significant differences in the maximal diameter and total volume between LPA group and INV group.Solid volume percentage and solid mass percentage were selected according to stepwise discriminant analysis.The accuracy of Bayes modes by using substitution method and cross validation method were 84.2% and 83.3%,respectively.Conclusion Solid volume percentage and solid mass percentage were important parameters for differentiating LPA from INV.Quantitative analysis of SSN was very helpful to preoperatively evaluate the subtypes and prognosis of lung adenocarcinoma by using 3DGCT segmentation technique.

Three-dimensional poly (epsilon-caprolactone)/silk sericin (PCL/SS) porous nanofibrous scaffolds were prepared by electrospinning. The structure and properties of the scaffolds were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and water contact angle instrument. Studies on cell adhension and proliferation were carried out by culturing human primary skin fibroblast cells (FEK4) on these scaffolds using SEM and MTS. The experimental results showed that the PCL/SS nanofibrous scaffolds with SS nanoparticles had porous non-woven mesh structure with nanofibrous cross-linked with each other. Fiber diameter was very uniform and precise, and the secondary structure of SS protein had not been changed. Furthermore, the capability of hydrophile increased with the SS addition, which improved FEK4 cells adhesion and proliferation on the scaffolds.
Biocompatible Materials ; chemistry ; Cell Adhesion ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; Microscopy, Electron ; Nanofibers ; chemistry ; Polyesters ; chemistry ; Sericins ; chemistry ; Silk ; chemistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds ; chemistry

Diabetes has become the world's major public health problem in the 21th century.Increasing attention has been paid to the importance of healthy sleep abroad,whereas less attention has been paid to it in China.Through literature study,this paper summarizes the current status of epidemiology and laboratory research on the relationship between sleep duration and incidence of type 2 diabetes,insulin sensitivity and blood glucose control both at home and abroad,and introduces the underlying mechanisms in order to provide evidence for further studies and the prevention and management of diabetes.

Objective:To compare and analyze the differences in the measurement of intra-abdominal pressure in different positions of critically ill patients treated with extracorporeal membrane oxygenation (ECMO) combined with prone position integration, with a view to finding a more optimal intra-abdominal pressure monitoring strategy, which can provide a theoretical basis for clinical diagnosis and treatment.Methods:Forty critically ill patients who underwent ECMO combined with prone position integrated treatment in the department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023 were selected by convenience sampling method using an own-control trial. The differences in intra-abdominal pressure between supine position with head elevated at 0°, 15°and 30°and prone position with head high and foot low slopes at 0°, 15°and 30°were compared and analyzed. Heart rate, respiration, mean arterial pressure and oxygen saturation were also compared in patients in different positions.Results:There were 29 males and 11 females in 40 patients with the age of (62.58 ± 17.99) years.The intra-abdominal pressure in supine position with head elevated at 30° was (12.45 ± 3.43) mmHg(1 mmHg=0.133 kPa), which was higher than that of 0° and 15° of (9.38 ± 2.52) and (10.70 ± 2.95) mmHg, and the differences were statistically significant ( t=4.56, 2.45, both P<0.05);the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05); the intra-abdominal pressure in prone position with head-high-foot-low slope of 30° was (12.92 ± 4.19) mmHg, which was higher than that of 0°and 15°of (9.67 ± 2.80), and (11.01 ± 3.10) mmHg, and the differences were statistically significant ( t=4.08, 2.32, both P<0.05); the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05).The differences in intra-abdominal pressure between groups of supine bed head elevation 0°, 15°, 30°and prone position with head high and foot low slopes 0°, 15°, 30°were not statistically significant (all P>0.05). The differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the supine position with head elevated at 0°, 15°and 30° were not statistically significant when compared within groups (all P>0.05); the differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the prone position with head elevated with feet and feet on low slopes at 0°, 15°and 30°were not statistically significant when compared within groups (all P>0.05); and the differences in supine position with head elevated at 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of heart rate, respiration, mean arterial pressure were not statistically significant (all P>0.05); supine bed head elevation 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of oxygen saturation between the groups, the differences were statistically significant ( Z=6.85, 6.82, 6.68, all P<0.05). Conclusions:Intra-abdominal pressure can be measured in the 15° prone position in critically ill patients treated with ECMO combined with prone position integration; the different positions have little effect on vital signs, but the prone position significantly improves oxygen saturation.