The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
Animals ; Superior Colliculi/physiology* ; Retinal Ganglion Cells/physiology* ; GABAergic Neurons/physiology* ; Mice, Transgenic ; Mice ; Optogenetics ; Visual Pathways/physiology* ; Mice, Inbred C57BL ; Photic Stimulation/methods* ; gamma-Aminobutyric Acid/metabolism* ; Male

【Objective】 To explore the application effect of traditional teaching combined with problem based learning (PBL) in the teaching of transfusion medicine taking the chapter of Human Leukocyte Antigen System and Testing in Clinical Blood Transfusion Testing Technique as an example. 【Methods】 Firstly, practical problems in chapter Human Leukocyte Antigen System and Testing were analyzed. Then, in response to the key and difficult points in the teaching of this chapter, examples were given to illustrate the practical application of traditional teaching combined with PBL in the teaching of Clinical Blood Transfusion Testing Technique from the aspects of teaching objectives, teaching processes, course implementation and implementation effects. The teaching effectiveness was evaluated through a questionnaire. 【Results】 Traditional teaching combined with PBL helped students grasp important knowledge and techniques, break down thinking barriers, grasp internal connections and characteristics, simplify the learning process, stimulate interest in learning and enhance team collaboration. Meanwhile, students' exploration and innovation abilities could be further cultivated through extracurricular expansion by teachers, thus achieving ideal teaching effect. The questionnaire showed that over 90% of the students consider that combining traditional teaching with PBL was beneficial for improving teaching effect. 【Conclusion】 In the teaching of transfusion medicine, adopting traditional teaching combined with PBL according to the textbook content can improve the teaching effect, which is beneficial for the cultivation of comprehensive talents.

Objective:Continuous glucose monitoring (CGM) technology is used to compare the advantages of insulin degludec (IDeg) as a basal insulin regimen compared with insulin glargine (IGlar) in the treatment of adult type 1 diabetes mellitus.Methods:30 adult patients with T1DM admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2019 to December 2020 were screened. According to the random number table method, the patients were randomly divided into two groups (insulin degludec group and insulin glargine group) at a ratio of 1∶1, respectively treated with IDeg, IGlar and aspartate insulin for 12 weeks. The main outcome measures were the coefficient of variation of blood glucose (CV), mean amplitude of glycemic excursions (MAGE), time in range (TIR), time above range (TAR) and time below range (TBR). The secondary outcome measures were mean blood glucose (MBG), standard deviation of blood glucose (SD), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h BG), hemoglobin A1c (HbA 1c), means of daily differences (MOOD), and the frequency of hypoglycemic events. Results:At 12 weeks of treatment, the HbA 1c, FPG, 2 h BG, MBG, SD, CV and MAGE of insulin degludec group were lower than those of insulin glargine group, with statistically significant difference (all P<0.05). The TIR in the insulin degludec group was significantly higher than that in the insulin glargine group [73(63, 75)% vs 43(28, 63)%, P<0.001], and the TAR was lower than that in the glycerine group [25(17, 23)% vs 35(33, 64)%, P=0.003]. From the curve spectrum of blood glucose level of the two groups, the stability of blood glucose in the insulin degludec group was better than that in the insulin glargine group. After 12 weeks of treatment, 8 cases (8/15) in insulin degludec group had HbA 1c<7.0%, and 4 cases (4/15) in insulin glargine group had HbA 1c<7.0%, without statistically significant difference ( P=0.264). There were 7 cases (7/15) in the insulin degludec group and 1 case (1/15) in the insulin glargine group who achieved high quality blood glucose control, with statistically significant difference ( P=0.035). At the 12th week of outpatient follow-up, the incidence of nocturnal hypoglycemic events in insulin degludec group was significantly lower than that in insulin glargine group (4/15 vs 11/15, P=0.027). Conclusions:Compared with insulin glargine, insulin degludec can achieve higher blood glucose compliance rate, lower blood glucose level and reduce blood glucose fluctuations in patients with type 1 diabetes.

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is rela-tively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.

【Objective】 To investigate the frequencies of HLA-B alleles in Jiangsu Han population from Chinese Marrow Donor Program (CMDP) Jiangsu Branch in 8 prefecture-level cities, compare and analyze the distribution of common susceptible alleles at HLA-B locus in 8 prefecture-level cities. 【Methods】 The HLA-B locus of 27 249 unrelated volunteers from CMDP Jiangsu Branch were genotyped by polymerase chain reaction–sequence based typing (PCR-SBT) method, and frequencies of HLA-B alleles of 8 prefecture-level cities were calculated and compared. 【Results】 A total of 145 HLA-B alleles were detected in Jiangsu Han population, among them 104, 113, 83, 88, 88, 85, 84, 72 HLA-B alleles were detected in Changzhou, Nanjing, Zhenjiang, Yangzhou, Huai’an, Suqian, Xuzhou, and Yancheng Han population, respectively. In general, the common alleles in Changzhou, Yangzhou and Zhenjiang were very similar, and the most common alleles were B^*46∶01, 13∶02, 40∶01 and 58∶01. The common alleles in Nanjing, Huai’an and Suqian were rather similar, and the most common alleles were B^*13∶02, 46∶01, 40∶01, 58∶01 and 51∶01. The common alleles in Yancheng were rather similar to Nanjing, Huai’an and Suqian, with only difference in the order of B^*40∶01 and B^*58∶01. The common alleles in Xuzhou were close to Nanjing, Huai’an and Suqian too, with only difference in the order of B^*40∶01 and B^*46∶01. 【Conclusion】 The results reflected the distribution of HLA-B alleles of Jiangsu Han population from 8 prefecture-level cities and the gene distribution was basically consistent with the regional distribution. The major difference in HLA-B locus in Jiangsu 8 prefecture-level cities was B ^* 13∶02 and B ^* 46∶01. The frequency of B ^* 13∶02 in Northern Jiangsu (Huai’an, Suqian, Xuzhou, Yancheng) is much higher than that of B ^* 46∶01, and that in Nanjing is slightly higher than the frequency of B ^* 46∶01, which is consistent with that in North China. The frequency of B ^* 46∶01 in Southern Jiangsu (Changzhou), Yangzhou and Zhenjiang is higher than that of B ^* 13∶02, which is consistent with that in South China. The polymorphism analysis of alleles at HLA-B locus in 8 cities in Jiangsu Province provided significant basic data for the study of the correlation between HLA-B locus genes and diseases, as well as the population genetics and anthropology in Jiangsu Han population.

Objective: To analyze the clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia by using Meta analysis. Methods: Thalidomide combined with conventional chemotherapy was treated as the experiment group, chemotherapy alone was treated as the control group. Thalidomide was taken 100mg once a day, oral administration. The literatures were retrieved from PubMed, Cochrane library, Embase, China Notional Knowledge Infrastructure (CNKI),Wanfang and VIP database. The data of the randomized controlled trial (RCT) conformed to inclusion criteria were extracted, and the quality was evaluated, and then StataMP 14.0 software was used to make a Meta analysis. Results: A total of 14 studies with 752 patients were included. The experiment group had a higher complete remission rate and the overall response rate compared with the control group, and the difference was statistically significant (RR= 1.61, 95% CI 1.36-1.90, P < 0.01; RR= 1.36, 95%CI 1.24-1.50, P < 0.01). The experiment group had a better efficacy in the improvement of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), basic fibroblast growth factor (bFGF) and bone marrow microvessel density (MVD) after the treatment compared with the control group, and the differences between the two groups were statistically significant (all P < 0.05), but there was no significant difference in the adverse events between the two groups (all P > 0.05). Conclusion Meta analysis showed that oral administration daily thalidomide 100 mg combined with conventional chemotherapy has a better clinical efficacy and antiangiogenic effect compared with chemotherapy alone, without the increase of adverse reactions.

Objective To OxplorO thO clinical Officacy of oral fluconazolO combinOd with clotrimazolO vaginal administration in thO trOatmOnt of candida vaginitis by mOta analysis. Methods FluconazolO combinOd with clotrima-zolO was sOlOctOd as OxpOrimOnt group and clotrimazolO alonO was sOlOctOd as control group. ThO randomizOd controllOd trials( RCTs) wOrO rOtriOvOd from PubMOd, CochranO library, EmbasO, China Notional KnowlOdgO infrastructurO (CNKI), WangFang and VIP databasO and rOfOrOncOs listOd in all studiOs. RCTs mOOting inclusivO studiOs wOrO includOd, thO data wOrO OxtractOd, thO quality was OvaluatOd and cross - chOckOd by two rOviOws indOpOndOntly according to CochranO Handbook for SystOmatic ROviOws of IntOrvOntions and thOn MOta -analysis was conductOd using Stata14.0 softwarO. Results A total of 15 studiOs and 1 792 patiOnts wOrO includOd.ThO OxpOrimOnt group had a highOr ovOrall OfficiOncy(OxpOrimOnt group in 96.13% and control group in 83.8% ),thO diffOrOncO was statistically significant (RR=1.13,95% CI 1.08~1.18,P<0.001). ThO rOcurrOncO ratO aftOr trOatmOnt( OxpOrimOnt group in 6.46% and control group in 20.74% ) had statistically significant diffOrOncO bOtwOOn thO two groups ( RR=0.31, 95% CI 0.21~0.46,P<0.001).Conclusion MOta analysis showOd that oral fluconazolO combinOd with clotrima-zolO vaginal administration has a bOttOr clinical Officacy.

Objective To Analyze the expression profiles of LncRNAs and mRNAs in ovarian epithelial cancer cell lines by gene mi-croarray, and then provide experimental evidences for investigating the function of LncRNAs associated with ovarian cancer. Methods The differentially expressed LncRNAs and mRNAs in ovarian epithelial cancer cell lines, such as A2780, HO8910 and SKOV3, and ovarian epithelial cell line HOSEpiC were analyzed by gene microarray. The differentially expressed mRNAs were further performed the KEGG pathway enrichment analysis. The expression levels of six candidate LncRNAs, which had significant difference between the o-varian epithelial cancer cell line and the ovarian epithelial cell line, were further verified by qRT-PCR. Results There were 227 up-regulated LncRNAs and 483 down-regulated LncRNAs in A2780, HO8910 and SKOV3 cell lines. The differentially expressed mRNAs in A2780, HO8910 and SKOV3 cell lines were mainly enriched in the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α( P<0.05) . The expression levels of PTPRG-AS1, CCNT2-AS1, XLOC 009869 and LINC01138 in ovarian epithelial cancer A2780, SKOV3 and OVCR3 cell lines were up-regulated (P<0.05), while those of RP11-252P19.2 and RP11-744I24.2 in ovarian epithelial cancer A2780, SKOV3, OVCR3 and 3AO cell lines were down-regulated ( P<0.05) . Conclusion The differentially expressed LncR-NAs and mRNAs in ovarian epithelial cancer cell lines may be obtained by gene microarray, and the differentially expressed mRNAs are associated with the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α, which may provide new targets for the diagnosis and treatment of ovarian cancer.

Objective: To explore the effects of Yueju pill on Nitricoxide-cyclic guanosine monophosphate (NO-cGMP) signaling in mouse hippocampus. Methods: Single dose of Yueju pill was administered, and mouse hippocampi were got out after administration for 12 min, 24 min, 30 min, 3 h and 24 h. The concentrations of NO and cGMP were detected by ELISA. Other mice were randomly divided into the following groups: control group (con), L-arg group (L-arg), Yueju pill group (YJ) and L-arg+ Yueju pill group (L-arg+YJ) . Control group was treated with saline, YJ group was treated with Yueju pill (13.5 g·kg-1), and L-arg group was treated with L-arg (750 mg·kg-1) . Tail suspension test (TST) was measured30 min after administration.Results:12 min after YJ administration, the concentration of NO was significantly lower than that in control group (P ＜ 0.05) and the concentration of c GMP was also significantly lower than that in control group (P ＜ 0.05) . In the TST test, the immobility time in YJ group was significantly shorter than that in control group (P ＜ 0.01), and the immobility time in L-arg+YJ group was significantly longer than that in YJ group (P ＜ 0.01) . In open field test (OFT), the spontaneous activity of mice were not affected by administering L-arg or YJ. Conclusion: Yueju pill may rapidly alleviate depression-like behaviors of mice through regulating NO concentration, then influencing downstream cGMP and activating the NO-cGMP signaling in cells.

Objective To explore the moisture absorption and related components of aqueous extract of Salviae Miltiorrhizae Radix et Rhizoma. Methods The hygroscopicity of aqueous extract of Salviae Miltiorrhizae Radix et Rhizoma and its water and alcohol elution parts separated by macroporous resin was measured, and the contained low molecular sugars (monosaccharides, oligosaccharide), polysaccharide, protein, amino acid, tannins and salvianolic acid B, etc. were analyzed. Results D101 macroporous resin was used for separation and purification of aqueous extract of Salviae Miltiorrhizae Radix et Rhizoma. The hygroscopicity of water elution parts was enhanced;carbohydrate, protein and other hydrophilic substances content increased; the content of salvianolic acid B was reduced to 1.76 mg/g. While the hygroscopicity and hydrophilic substances of alcohol elution parts were greatly reduced; the content of salvianolic acid B increased to 146.57 mg/g. Conclusion The hygroscopicity of aqueous extract of Salviae Miltiorrhizae Radix et Rhizomais closely related to the contained strong hydrophilic components, such as low molecular sugars, etc. Using D101 macroporous resin to purify aqueous extract of Salviae Miltiorrhizae Radix et Rhizoma can not only effectively gather the contain phenolic acids active ingredients, but also sharply decrease the extract yield and extract moisture absorption.