The degranulation of mast cells represents a pivotal e-vent in the allergic disorders.The Src family kinases(SFKs)are as a starting signal in the activation of mast cell.Lyn,Fyn and Syk play important regulatory role in the degranulation of mast cells.Regulating SFKs can reduce the degranlation process and inhibit the allergic disorders.Therefore,SFKs inhibitors can be potential drugs in the allergy.It is necessary to study the targeted medicine of SFKs,which will be a new direction of drug develop-ment.

Background Refractive lens exchange is one of corrective surgeries for high myopic eyes and is concerned in clinic recently. Its clinical value is worthy of consideration. Objective This study was to investigate the efficacy and safety of refractive lens exchange for high myopic eyes. Methods Phacoemulsification and intraocular lens implantation was performed on 124 eyes of 65 patients with high myopia. The mean age of these patients was 51. 4±8. 57 years old,and the preoperative corrected visual acuity was 4. 11±0. 51. The mean spherical equivalent was ( -20. 17±5. 34) D. The mean axial length was (31. 33±2. 08) mm and intraocular lens power 2. 88 D. The follow-up time was 31 months. The uncorrective visual acuity, best corrective visual acuity, the spherical equivalent lens and complications were observed after operation. Written informed consent was obtained prior to the surgery. Results The uncorrective visual acuity improved after the operation in all the eyes. The uncorrective visual acuity was ≥0.5 in 15 eyes(12% ). The best corrected visual acuity improved in 114 eyes (92% ) following the surgery and that of 64 eyes (51. 6% ) was 2s 0. 5. The mean postoperative spherical equivalent was ( -2. 57 ± 1. 76 ) D in the entire follow-up duration. Posterior capsular opacification was found in 58 eyes (46. 7% ) and received laser capsulotomy. Retinal detachment occurred in 4 eyes throughout the follow-up period. Conclusion Refractive lens exchange is an effective and safe method for high myopic eyes. But preoperative fundus examination and long-term postoperative follow-up should be carried out to prevent the complications.

OBJECTIVETo investigate the main factors that influence the results of sperm alkaline single-cell gel electrophoresis (SCGE), optimize the conditions, and standardize its procedures.

METHODSUsing alkaline SCGE, we detected the DNA fragments of sperm treated with different concentrations of H2O2 and determined the influences of the number of agarose gel layers, pH during DNA unwinding and electrophoresis, the time of DNA unwinding and electrophoresis, and cumulative sperm number on the results of sperm alkaline SCGE. Then we optimized the procedures, analyzed the repeatability of the optimized method, and examined 40 semen samples using the method.

RESULTSThree agarose gel layers could reduce the background. The optimal pH during DNA unwinding and electrophoresis was 10, and the best times for DNA unwinding and electrophoresis were 40 min and 30 min, respectively. Fifty sperm were adequate to ensure the reliability of the results. Based on the percentage of tail DNA, the intra- and inter-assay repeatabilities of the optimized sperm alkaline SCGE were 3.12% and 7.13%, and by the DNA damage score, they were 2.38% and 6.09%, respectively. Sperm DNA fragments were significantly increased in the infertile patients with oligoasthenoteratozoospermia as compared with healthy fertile males (P <0.05).

CONCLUSIONThe optimized sperm alkaline SCGE, highly repeatable and easy to be standardized, can be applied to the clinical detection of sperm DNA fragmentation in infertile men.

Asthenozoospermia ; genetics ; Comet Assay ; standards ; DNA Damage ; DNA Fragmentation ; Humans ; Hydrogen Peroxide ; toxicity ; Male ; Oligospermia ; genetics ; Oxidants ; toxicity ; Reproducibility of Results ; Sperm Count ; Spermatozoa ; drug effects ; enzymology ; Time Factors

Objective To study the differences between the animal model of pulmonary injury/ fibrosis induced by using paraquat and that induced by using bleomycin in mice in order to establish an ideal mouse pulmonary fibrosis model.Methods Thirty healthy and 8 ～ 10 weeks old male C57BL/6J (C57) mice were randomly (random number) divided into paraquat group (n =10),bleomycin group (n =10),and control group (n =10).Paraquat ( 10 mg/kg) was given to mice intraperitoneally once every three days for 5 times in paraquat group.Bleomycin was injected into trachea of mice in a dose of 3 mg /kg in bleomycin group.The mice were sacrificed 7 days,14 days and 21 days after administration of drug.The general physical condition,body weight and pulmonary pathological changes were observed.Data were analyzed with SPSS13.0 statistical package.The comparison was made between two groups with mann -whitney U- test.Results Both agents could induce pulmonary injury and fibrosis.After comparison of survival rate,body weight,pulmonary histopathological change and rate of successful modelling,the repeated low - dose of paraquat injected intraperitoneally was proved to be a method of more simple and effective with high success rate of modeling in comparison with the conventional technique of intratracheal injection of bleomycin.Conclusions By the comparison between two methods of establishing pulmonary injury and fibrosis models in mice,the method of repeated low - dose intraperitoneal injection of paraquat is superior over the bleomycin - induced method in respect of higher rate of successful modelling.

Objective To investigate the efficacy and safety of dexmedetomidine on prevention of emergence agitation in adult patients during recovery period after abdomen surgery.Methods 1 20 ASA I -II patients scheduled for elective abdominal surgery under general anesthesia were randomly divided into three groups:dexmedetomidine group (group A),midazolam group (group B)and the saline control group (group C),40 cases in each group.40min before the end of surgery,dexmedetomidine 0.6μg/kg was continued intravenous infusion 1 0min in group A,midazo-lam 30μg/kg and 1 mL physiological saline were respectively intravenously injected in group B and group C.The post-operative recovery room (PACU)of restlessness,sedation,blood pressure,SpO2 and extubation time were observed. Results In of midazolam group,the time of anesthesia recovery[(1 8.2 ±1 .9)min],extubation[(32.1 ±3.9)min] and PACU staying[(48.7 ±3.1 )min]were significantly longer compared with the dexmedetomidine group[(1 3.1 ± 2.4)min,(26.5 ±2.2)min and (39.8 ±3.4)min,P =0.023,0.040 and 0.003]and the saline group[(1 2.6 ± 2.3)min,(24.8 ±2.9)min and (38.6 ±4.3)min,P =0.01 7,P =0.023 and P =0.001〗.The postoperative seda-tion scores of dexmedetomidine [(2.3 ±0.2 )points,P =0.025 ]and midazolam group [(2.4 ±0.1 )points,P =0.020]were significantly higher than the saline control group[(1 .1 ±0.5)points].The postoperative agitation score of dexmedetomidine (1 .3 ±0.5)points was lower than midazolam group [(2.5 ±0.5)points,P =0.01 1 ]and the saline control group[(2.4 ±0.6)points,P =0.020].HR and MAP of three groups at 2 min before extubation were observed,in the immediate extubation and at 5 min after extubation,the HR of dexmedetomidine group[(62.7 ± 4.1 )times/min,(67.3 ±3.4)times/min and (63.2 ±4.3)times/min]was significantly delayer than midazolam group [(72.3 ±3.4)times/min,(84.9 ±5.3)times/min and (82.1 ±3.1 )times/min],(P =0.002,P =0.001 and P =0.001 )and the saline control group [(73.6 ±2.9 )times/min,(85.3 ±4.7 )times/min and (83.3 ± 4.5)times/min],(P =0.001 ,P =0.023 and P =0.038)at the three time.In the immediate extubation,the MAP of patients in dexmedetomidine group[(87.3 ±4.2)mmHg)]was lower than midazolam group[(93.1 ±4.3)mmHg, P =0.001 ]and the saline control group[(95.6 ±5.8)mmHg,P =0.001 ].At 5 min after extubation,the MAP of patients in both of dexmedetomidine[(84.5 ±3.1 )mmHg)]and midazolam[(85.1 ±2.9)mmHg]group were lower than that in the saline control group[(92.3 ±4.6)mmHg,P =0.023 and P =0.038〗.Conclusion Dexmedetomi-dine could be one of the ideal drug to relieve emergence agitation in adult patients during recovery period after abdo-men surgery and the curative effect is better than midazolam.

Background The aspheric intraocular lenses(IOLs)can reduce ocular spherical aberration to some degree.However,the clinical effect depends more on the IOL proper alignment.It becomes more important to study the IOL position in eye,Objective This study was to analyze the position alteration of IOL after phacoemulsification combined with implantation of one-piece soft IOLs.Methods In this prospective control study,80 eyes of 40 patients with age-related cataract were enrolled.The phacoemulsification with IOL implantation was performed in all the eyes.Decentration and tilt of IOL in the nasal superior,superior temporal,inferior temporal and nasal inferior quadrants(the intersection point of the system optical axis and the IOL maximum cross plane were regarded as the ordinate origin)were measured by rotating Scheimpflug camera(Pentacam Oculus)in 3 months postoperatively under the mydriasis condition.Written informed consent was obtained from each subject prior to this trial.Results In the right eye group,the IOL decentered toward temporal in 26 eyes(65％)and infratemporal in 16 eyes(40％).IOLs tilted temporally in the horizontal plane in 37 eyes(92.5％)and tilted inferiorly in the vertical plane in 34 eyes(85.0％).In the left eye group,IOLs decentered temporally 33 eyes(82.5％)and 20 IOLs (50％)infratemporally,IOLs tilted temporally in the horizontal plane in 37 eye(92.5％)and 36 IOLs(90％)tilted inferiorly in the vertical plane.There was no statistical difference for the intercomparsion of horizontal/vertical decentration in various quadrant in the right eye(F =0.221,0.792,P＞0.05).The obvious elevated horizontal decentration was found in the supertemporal and infratemporal quadrants compared with supernasal quadrant in the left eyes but there was no significant difference in the vertical decentration among 3 quadrants(F=0.576,P＞0.05).Decentrations were positively correlated with the tilt in both horizontal and vertical plane(right eye horizontal plane:r=0.374,P=0.002;right eye vertical plane:r=0.402,P=0.001 ;left eye horizontal plane:r=0.377,P=0.002；left eye vertical plane:r=0.347,P=0.002).Conclusions The one-piece soft IOLs(Adapt AO)decenter toward temporal mostly in 3 months after surgery,especially infratemporally in the eye.And the optical axis of the IOL tilt toward infratemperol mostly in both right and left eyes.The decentration and tilt are consisted in the corresponding direction between the right and left eyes.The position of the IOLs showed mirror symmetry between right and left eyes.The IOLs decentration show the positively correlation to tilt whatever in horizontal and vertical plane.

AIM: To study caspase-9 expression on rat retina in the process of chronic elevation of IOP and the changes with the application of amino guanidine (AG), thus to investigate potential protective function of AG to rat retina with chronic elevation of IOP.METHODS: Immunohistochemistry, RT-PCR and Western blot were used to observe retinal morphology and expression of caspase-9 at different time points of rat with chronic IOP elevation, both affected or not affected by the application of AG.RESULTS: Compared with control group, as time passed retina of experimental group gradually had detectable morphological changes. On 21st day of chronic IOP elevation, retinas became thinner and the quantity of retinal ganglion cells (RGCs) decreased; caspase-9 expression increased, consistent with the morphological changes. The group using AG presented relatively smaller morphology changes and less expression of caspase-9.CONCLUSION: Apoptosis-related gene caspase-9 played a part in the process of chronic IOP elevation; AG protects retina by down-regulating expression of caspase-9.

In 2011, the FDA approved ipilimumab, the first immune checkpoint inhibitor(ICI), targeting CTLA-4, opening the field of immune checkpoint therapy (ICT). ICIs can induce durable clinical responses and improve survival in selected population. However, significant challenges still remain, including mechanisms of resistance, patient selection, management of serious immune-related adverse events, and rational therapeutic combinations. This review surveys the current understanding of response and resistance to ICIs and proposes a path forward to improving efficacy and minimizing toxicities.

OBJECTIVETo investigate whether the p38 mitogen-activated protein kinase (MAPK) signaling pathway mediates advanced oxidation protein products (AOPPs)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells.

METHODSHuman proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA) were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using Western blotting. Western blotting and quantitative RT-PCR were used to examine the protein and mRNA expressions of EMT markers E-cadherin and vimentin and endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to AOPP exposure. The cells treated with AOPPs following pretreatment with salubrinal (an inhibitor of endoplasmic reticulum stress) were also examined for expressions of p38 MAPK and phosphorylated p38 MAPK.

RESULTSAOPP treatment induced the phosphorylation of p38 MAPK in HK-2 cells. AOPP-induced decrease in E-cadherin expression and overexpression of vimentin and GRP78 were partly inhibited by pretreatment of the cells with SB203580. Salubrina partly suppressed AOPP-induced phosphorylation of p38 MAPK in the cells.

CONCLUSIONp38 MAPK signaling pathway, which is regulated by endoplasmic reticulum stress, might mediate AOPP-induced EMT in HK-2 cells.

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.
Bilirubin ; China ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Hyperbilirubinemia, Neonatal ; Infant, Newborn ; Retrospective Studies