Objective To investigate the mechanism of retinal injury in rats caused by light-emitting diodes(LEDs)with different color rendering indexes(CRIs).Methods Totally 20 Sprague-Dawley rats were randomly divided into nor-mal control(NC)group(sunlight),low CRI(CRI-L)group(blue light),medium CRI(CRI-M)group(conventional LED),and high CRI(CRI-H)group(full-spectrum LED),with 5 rats in each group,exposed to light for 12 hours daily for 4 consecutive weeks.Hematoxylin & eosin staining was used to assess morphological changes in the retina.Dihydroethidi-um staining was employed to detect the levels of reactive oxygen species(ROS)in retinal tissues.The messenger ribonu-cleic acid(mRNA)expressions of NOD-like receptor family pyrin domain containing protein 3(NLRP3),Gasdermin D(GSDMD)and Caspase-1 were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR),and their protein expressions were measured through immunohistochemical staining.Environmental light spectra were measured using a spectroradiometer.Results Rats in the CRI-L group showed the thinnest retina,followed by the CRI-M group and CRI-H group.The fluorescence intensity of ROS in the NC group,CRI-L group,CRI-M group and CRI-H group was 1.000±0.046,25.060±1.732,14.530±3.776 and 1.821±0.587,respectively.The ROS level in the CRI-H group was significantly lower than that in the CRI-L group and CRI-M group(both P＜0.05).RT-qPCR showed that the relative mRNA expression of NL-RP3 in the NC group,CRI-L group,CRI-M group and CRI-H group was 1.004±0.005,4.004±0.716,2.027±0.303 and 0.741±0.069,respectively;the relative mRNA expression of Caspase-1 was 1.010±0.006,4.337±0.345,2.268±0.058 and 0.713±0.021,respectively;the relative mRNA expression of GSDMD was 1.000±0.000,2.938±0.559,1.955±0.166 and 1.213±0.051,respectively.Compared with the NC group,the relative expressions of NLRP3,Caspase-1 and GSDMD in the CRI-L group and CRI-M group significantly increased(all P＜0.05).The immunohistochemical staining results showed that the fluorescence intensity of NLRP3 in the retina of rats in the NC group,CRI-L group,CRI-M group and CRI-H group was 0.379 4±0.002 2,0.400 7±0.011 4,0.379 0±0.006 9 and 0.377 0±0.007 5,respectively;the fluorescence intensity of Caspase-1 was 0.367 2±0.005 8,0.442 6±0.041 1,0.382 4±0.011 9 and 0.380 6±0.006 5,respectively;the fluorescence intensity of GSDMD was 0.159 5±0.013 4,0.167 5±0.011 9,0.397 6±0.014 3 and 0.377 2±0.022 8,respec-tively.Compared with the NC group,rats in the CRI-L group showed increased fluorescence intensity of NLRP3 and Caspase-1,and rats in the CRI-M and CRI-H showed increased fluorescence intensity of GSDMD(all P＜0.05).The spec-tral comparison revealed that the CRI-H group had a broader spectral coverage and a distribution closer to natural light spectra.Conclusion Conventional LED exposure can induce a decrease in retinal thickness,upregulate the ROS expres-sion in retinal tissues,and increase the expression levels of NLRP3,Caspase-1 and GSDMD.High CRI full-spectrum LEDs can mitigate pyroptosis through the ROS/NLRP3 pathway by optimizing their spectral distribution,offering better biosafety.

Generally, small for gestational age(SGA) infants will catch up with growth after birth, but some SGAs fail to show enough catch-up growth, leading to physical growth backwardness, and the risk of metabolic diseases in adult offspring increases. The application of exogenous growth hormone replacement therapy can ensure and promote the occurrence of SGA catching up with growth. However, as growth hormone exerts therapeutic effects in related clinical diseases, clinical attention is gradually being paid to whether growth hormone may bring long-term risks. This article aims to review the efficacy and potential risks of growth hormone treatment for SGA.

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Objective:To establish neurodevelopmental mice model of schizophrenia(SZ) with prepulse inhibition(PPI) deficits and investigate the effectiveness of olanzapine on PPI disruption.Methods:On the 9th day of pregnancy of SPF grade C57BL/6 mice, female mice were injected with polyinosinic acid poly (I∶C) (6 mg/kg) through tail vein for immune stimulation. The stress model was constructed by chronic unpredictable mild stress 30-40 d after birth (PND30-40). The offspring mice were divided into pregnancy immune stimulation + adolescent stress group (P + S + group), pregnancy immune stimulation group (P + S- group), adolescent stress group (P-S+ group) and non stimulation group (P-S-group), with 18 mice in each group. The mice in P+ S+ group were divided into OLZ intervention group (OLZ group) and non-OLZ intervention group (non-OLZ group), with 9 mice in each group. The PPI function of mice was detected by acoustic startle reflex test after modeling and OLZ intervention. Adopt StatView Version 5.0 software for data analysis, and multi factors analysis of variance was used to test the main effect, interactive effect and simple effect of each factor.Results:The main effects of maternal Poly(I: C) immune activation and pubertal chronic unpredictable stress were significant( F(1, 330)=47.72, P<0.01), and there was a significant interaction between the two factors( F(1, 330)=14.80, P<0.01), simple effect analysis showed that average percent prepulse inhibition (PPI%) in P+ S+ group((15.42±6.13)%) was significantly decreased compared with groups of P+ S-((27.33±4.58)%), P-S+ ((31.17±3.97)%) and P-S-((47.14±12.28)%)(all P<0.01). There was significant gender difference in Prepulse inhibition(PPI)score( F(1, 396)=61.94, P<0.01), in male and female mice, average startle reactivity of Pulse under Prepulse+ Pulse influence of distinct intensities was significantly different( F(1, 198)=18.68, 18.44, P<0.01), and the maternal Poly(I∶C) immune activation had a significant main effect( F(1, 198)=32.18, 12.58, P<0.01) and interaction with pubertal chronic unpredictable stress( F(1, 198)=34.54, 11.39, P<0.01), simple effect analysis suggested that the average startle reactivity of Prepulse+ Pulse in P+ S+ group(0.47±0.12) was significantly higher than other three groups(P+ S-: 0.36±0.11, P-S+ : (0.25±0.22), P-S-: (0.31±0.19)) in male mice( P<0.01) and in P-S+ group was significantly higher than the other three groups in female mice ( P<0.01). OLZ treatment could efficiently reverse the deficits on PPI by increasing PPI%( F(1, 165)=18.24, P<0.01), OLZ could reduce PPI score in male "dual-hit" model mice( F(1, 102)=21.81, P<0.01)and raise it in female( F(1, 102)=4.88, P<0.05). Conclusion:OLZ can reverse PPI deficits in schizophrenic neurodevelopmental model mice, and in the evaluation of PPI function in the model mice through PPI of acoustic startle reflex, PPI% has better stability and reactivity to OLZ intervention.

Objective:This study aims to explore the structural characteristics of the abnormal brain cortex in patients with autism by analyzing the neuroanatomical differences between patients with autism and the healthy controls.Methods:This study analyzed the brain imaging data of patients with autism ( n=525) and healthy controls ( n=569) extracted from the database of the Autism Brain Imaging Data Exchange (ABIDE) which collected data from 20 sites around the world. The cerebral cortex thickness was estimated using the FreeSurfer software based on the data of brain structure and was compared between patients with autism and the healthy controls using the t test. At the same time, according to their age, all participants were divided into three groups, which were younger than 12 years old group(150 patients and 151 controls), 12 to 18 years old group (210 patients and 233 controls), and older than 18 years old group (159 patients and 183 controls), and the cortical thickness was compared between patients with autism and healthy controls in different age groups using the t test respectively. Results:Based on the comparison of the thickness of the cerebral cortex between the autism group and the control group, it was found that compared with the control group, patients with autism showed a significant increase in cortical thickness in the occipital face area of both left and right sides of the brain (left side: size=1 043.95 mm 2, Z=4.31, MNI coordinates: x=-13.1, y=-102.4, z=2.4; right side: size=1 364.13 mm 2, Z=5.14, MNI coordinates: x=14.4, y=-101.3, z=3.1) and significant atrophy of cortical thickness at the posterior part of the superior frontal gyrus on the right side of the brain (size=485.86 mm 2, Z=4.71, MNI coordinates: x=6.8, y=-13.1, z=61.6). Comparisons of cerebral cortical thickness in different age groups found that patients younger than 12 years old showed a significant reduction in cortical thickness in the middle and posterior right superior frontal gyrus (right side: size=914.44 mm 2, Z=4.86, MNI coordinates: x=19.7, y=32.4, z=41.1) and inferior temporal gyrus (left side: size=638.16 mm 2, Z=-4.36, MNI coordinates: x=-34.7, y=-32.5, z=-22.8) compared to the healthy controls of the same age. Patients within 12 to 18 years old showed a reduction in the cortical thickness of the posterior upper frontal gyrus and an increase in the occipital facial area compared to the corresponding healthy controls. No significant difference in the thickness of the cortex was found between patients older than 18 years and the healthy controls of the same age. Conclusion:Abnormal cortical thickness in the occipital face area and posterior part of the superior frontal gyrus could be the characteristics of neurodevelopment in patients with autism, especially in younger children with autism.

Objective:This study aims to explore the structural characteristics of the abnormal brain cortex in patients with autism by analyzing the neuroanatomical differences between patients with autism and the healthy controls.Methods:This study analyzed the brain imaging data of patients with autism ( n=525) and healthy controls ( n=569) extracted from the database of the Autism Brain Imaging Data Exchange (ABIDE) which collected data from 20 sites around the world. The cerebral cortex thickness was estimated using the FreeSurfer software based on the data of brain structure and was compared between patients with autism and the healthy controls using the t test. At the same time, according to their age, all participants were divided into three groups, which were younger than 12 years old group(150 patients and 151 controls), 12 to 18 years old group (210 patients and 233 controls), and older than 18 years old group (159 patients and 183 controls), and the cortical thickness was compared between patients with autism and healthy controls in different age groups using the t test respectively. Results:Based on the comparison of the thickness of the cerebral cortex between the autism group and the control group, it was found that compared with the control group, patients with autism showed a significant increase in cortical thickness in the occipital face area of both left and right sides of the brain (left side: size=1 043.95 mm 2, Z=4.31, MNI coordinates: x=-13.1, y=-102.4, z=2.4; right side: size=1 364.13 mm 2, Z=5.14, MNI coordinates: x=14.4, y=-101.3, z=3.1) and significant atrophy of cortical thickness at the posterior part of the superior frontal gyrus on the right side of the brain (size=485.86 mm 2, Z=4.71, MNI coordinates: x=6.8, y=-13.1, z=61.6). Comparisons of cerebral cortical thickness in different age groups found that patients younger than 12 years old showed a significant reduction in cortical thickness in the middle and posterior right superior frontal gyrus (right side: size=914.44 mm 2, Z=4.86, MNI coordinates: x=19.7, y=32.4, z=41.1) and inferior temporal gyrus (left side: size=638.16 mm 2, Z=-4.36, MNI coordinates: x=-34.7, y=-32.5, z=-22.8) compared to the healthy controls of the same age. Patients within 12 to 18 years old showed a reduction in the cortical thickness of the posterior upper frontal gyrus and an increase in the occipital facial area compared to the corresponding healthy controls. No significant difference in the thickness of the cortex was found between patients older than 18 years and the healthy controls of the same age. Conclusion:Abnormal cortical thickness in the occipital face area and posterior part of the superior frontal gyrus could be the characteristics of neurodevelopment in patients with autism, especially in younger children with autism.

Objective To investigate the differential expression of microRNA (miRNA) in schizophrenia (SZ) patients,and explore the comorbidity of SZ and depression disorder based upon miRNA expression.Methods Affymetrix array analysis was used to investigate the differentially expressed miRNA in SZ patients firstly,and then quantitative real-time polymerase chain reaction (qRT-PCR) was further carried out to confirm the selected miRNA in peripheral blood mononuclear cells of 40 SZ patients,whom were administered by Positive and Negative Syndrome Scale (PANSS) and the selected miRNAs in depression disorder patients has also been confirmed by Affymetrix array analysis and qRT-PCR in our previous studies.Results Affymetrix array analysis indicated that there existed 33 miRNAs which differentially expressed (32 up-regulated and 1 down-regulated) compared with normal controls.qRT-PCR results suggested that the expression of 8 miRNAs (miR-1273d,miR-1303,miR-3064-5p,miR3131,miR-3687,miR-4428,miR-4725-3p and miR-5096) were significantly up-regulated in SZ;the miRNA differentially expressed in depression disorder patients also had differential expression in SZ patients (P＜0.05).There were significant correlation between the miRNAs differentially expressed in depression disorder patients and in SZ patients (P＜0.01).MiR-1972 differentially expressed in depression disorder patients had significant positive correlation with the positive symptoms of PANSS (P＜0.05),and miR-26b was positively correlated with composite factor (P＜0.05).Conclusion Comorbidity of SZ and depression disorder is observed not only on the clinical symptoms,but on the molecular genetic basis.

Objective To evaluate the effect of case-based learning combined with standardized patients in probation of nuclear radionuclide therapy.Methods 360 interns were randomly assigned separately into CBL+SP group and LBL group (180 people),case based on SP as the center of clinical teaching mode was used for CBL+SP group,while traditional classroom teaching mode was used for LBL group.Theoretical test,case analysis and teaching satisfaction survey were used to evaluate the two teaching mode,using SPSS 20.0 software for statistical analysis of the data.t test was used for two independent samples of both theoretical test and case analysis and chi-square test was used for teaching satisfaction survey.Results The score of theory and case analysis of CBL+SP group was higher than that of LBL group,and the difference had statistical significance [(83.26 ± 4.18) vs.(80.36 ± 3.62),t=-7.041,P=0.000;(85.79 ± 4.15) vs.(81.26 ± 3.96),t=-10.844,P=0.000].Satisfaction survey showed that satisfaction degree of CBL+SP group in stimulating and training the correct clinical thinking,grasping the information skills and cultivating their ability to analyze and solve the problem was higher than that of LBL group,and the difference had statistical significance (x2=40.319,x2=33.620,x2=23.493,x2=23.283;P=0.000).Conclusion Case-based learning combined with standardized patients in probation of nuclear radionuclide therapy can obtain satisfactory teaching effort.