Objective To study the dynamic changes of left ventricular hypertrophy with age found in spontaneously hypertensive rats (SHR). Methods Forty-five male SHR and thirty-five male Wistar Kyoto rats (WKY), which were four-week-old and specific-pathogen free, were observed continuously for 42 weeks. At 6,8,12,18,24,32 and 42 weeks of age, cardiac structure and function were examined by echocardiography, and systolic blood pressure was measured by tail cuff method; At the same time points, left ventricular mass index (LVMI) was calculated. The morphology of left ventricle was microscopied by HE staining, genes ANP and β-MHC were detected by RT-qPCR. Results The systolic blood pressure of SHR increased rapidly during the period from 6th to 12th weeks, and was significantly higher than that of WKY at 12 weeks (P＜0.05), after that the blood pressure of SHR increased slightly and slowly. With age and blood pressure changes, left ventricular hypertrophy gradually developed in SHR.The related hypertrophic indexes,interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT),transverse diameter of myocardial cell (TDM) and LVMI all showed characteristic changes. Correspondingly, the expression of hypertrophy-related genes ANP and β-MHC in SHR showed age- and blood pressure-dependent dynamic changes. Conclusions The left ventricular hypertrophy in SHR is characterized by the dynamic changes with aging and change of blood pressure.

Objective To observe the injury of intestinal mucosal barrier and the expression of autophagy protein in colon tissue of rats with chronic renal failure. Methods Thirty SPF healthy male SD rats were randomly divided into sham operation group (10 rats) and model group (20 rats). The model group was given adenine 200 mg/(kg·d) by gavage for 4 weeks after left nephrectomy. The general conditions of rats were observed. Serum, renal tissue and colon tissue samples were collected at 4 and 8 weeks after gavage. The levels of serum creatinine, urea nitrogen, TNF-α, IL-6 and LPS were measured by ELISA. Renal and colon tissue were examined by HE staining and microscopy. The protein expressions of LC3, beclin-1, ZO-1 and claudin-1 were detected by Western blot. Results Compared with the sham operation group, the model group rats gradually showed a slow response to external stimuli, slow action, withered and yellow hair color, dull luster, pale conjunctiva and slow weight gain. The levels of serum creatinine, urea nitrogen and inflammatory factors in the model group were all higher than those in the sham operation group, and increased at 8 weeks compared with 4 weeks (P＜0.05). Renal pathology in the model group showed renal tubular dilatation, lymphatic and monocyte infiltration, glomerulosclerosis and interstitial fibrosis. Histopathology of colon in model group showed atrophy and collapse of intestinal villi, infiltration of inflammatory cells in mucosal layer and aggravation of pathological changes, which was more serious at 8 weeks than at 4 weeks. The expression of LC3Ⅱ/Ⅰ, Beclin-1, ZO-1 and Claudin-1 in the model group decreased as compared to those of sham operation group(P＜0.05), and much decreased at 8 weeks as compared with 4 weeks (P＜0.05). Conclusions Autophagy disorder may be a potential mechanism causing intestinal mucosal barrier injury in rats with chronic renal failure.

Objective To investigate the pathogenic gene mutations and clinical characteristics in a patient with compound heterozygote gene mutations in luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. Methods Clinical features, laboratory data and radiologic manifestations were collected. The whole exon was sequenced. Pathogenicity of the mutations was evaluated by using the Mutation Taster, PANTHER software. The relationship of the splice site mutation and the phenotype of the LHCGR gene was investigated by literature review. Results 1)The patient presented with a micropenis.2)The level of gonadotropins was high but level of testosterone was low. 3)Compound heterozygotic mutations including a splicing mutation (c.233+1G＞A) and a missense mutation (c.547G＞A) were identified in LHCGR gene. Both variations were derived from his parents with normal epitope so it was the first case reported in this familiy. 4)The patient had a good response to testosterone therapy. Conclusions LHCGR mutation may cause micropenis. Our report expands the spectrum of clinical manifestations and mutation of LHCGR gene.

Objective To evaluate the effect of icariin on sevoflurane-induced postoperative cognitive dysfunction (POCD),and to explore its potential mechanism. Methods The mice were divided into control group, model group(sevoflurane anesthesia + laparotomy were used to establish a mouse POCD model), icariin group, PI3K inhibitor group, icariin + inhibitor group, PI3K activator group, with 12 rats in each group. Conditional fear test and Y maze test were used to evaluate cognitive dysfunction in mice; ELISA method was used to detect the levels of serum TNF-α, IL-1β and BDNF; the hippocampal tissue was taken, Nissl staining was used to observe the changes of neuron morphology; TUNEL staining was used to detect neuronal apoptosis rate; the expression levels of M1 and M2 activated microglia and their markers were detected by immunofluorescence method; Western blot was used to detect the expression of TNF-α, IL-1β,IL-10, GSK-3β phosphorylated protein and Bcl-2. Results Compared with the control group, mice of model group showed cognitive impairment, severe hippocampal neuron impairment and apoptosis, the pro-inflammatory response mediated by M1 polarization of microglia in the hippocampus was more intensive than the anti-inflammatory response mediated by M2 polarization. The expression of PI3K/Akt-GSK-3β pathway and its mediated anti-inflammatory and anti-apoptotic proteins decreased (P＜0.05). Icariin and PI3K activator intervention promoted the PI3K/Akt-GSK-3β pathway and its anti-inflammatory and anti-apoptotic responses, and promote the anti-inflammatory response mediated by M2 polarization of hippocampal microglia, alleviated the impairment and apoptosis of hippocampal neurons, and improved cognitive function impairment of mice (P＜0.05). PI3K inhibitors could weaken the above-mentioned effects of icariin (P＜0.05). Conclusions The effect of icariin on improving the apoptosis of hippocampal neurons and cognitive impairment in POCD mice may be related to promoting the activation of PI3K/Akt pathway and enhancing the anti-inflammatory response mediated by M2 polarization of microglia.

Objective To investigate the gene carrying rate,gene mutation type and hematological characteristics of thalassemia in Dai nationality population of Dehong Prefecture, Yunnan Province. Methods A total of 591 Dai nationality gestational age population in Dehong were tested for thalassemia gene by next-generation sequencing technology. The sensitivity and specificity of the hemoglobin electrophoresis and blood routine tests were performed. Results A total of 289 cases (48.90%) were positive for thalassemia gene. Among them,231 cases were classified as α-thalassemia(39.09%) and 89 cases were β-thalassemia(15.06%). Five α-thalassemia genotypes and seven β-thalassemia genotypes were detected. For α-thalassemia, --^SEA showed comparatively lower values for MCV and MCH; α^CSα showed comparatively lower values for Hb A2 (P＜0.05). For the β-thalassemia,CD 26 (G＞A)had significantly lower Hb A values,and higher MCH values(P＜0.05). A new cut-off value for the thalassemia with the highest accuracy was proposed(MCV 83.55 fL,MCH 27.95 pg). Conclusions Thalassemia is common in Dai nationality population of Dehong. The most frequently identified types are －α^3.7 and CD 26 (G＞A).

Objective To investigate the effect of balanophora polysaccharide (BPS) on neuro-autophagy and its therapeutic effect on spinal cord injury. Methods The rats were randomly divided into sham operation group(sham, n=10),model group(SCI, n=15,which were established according to the Allen's weight-striking method), and the BPS treatment group(BPS, n=45),which were given intra-gastrically with low, medium and high dose of BPS solution for 14 days). The BBB scores were measured to evaluate motor function. Hematoxylin-Eosin and Nissl staining was used to observe the morphological changes. The expression of autophagy markers of Beclin 1, LC3-Ⅱ and p62 was detected by Western blot. Results Compared with the sham operation group,the curve of BBB score-time in SCI group was significantly lower and the injury was severer(P＜0.05). In SCI group, the dorsal white matter and central gray matter of spinal cord were seriously injured with obvious cavity. Further observation showed that the number of neurons in SCI group was significantly decreased; the structure of cell body was incomplete. The result of Western bolt showed that the relative change of LC3 Ⅱ /Ⅰ and p62 was up-regulated on day 1,7 and 14, the highest expression of both protein was found on day 7(P＜0.05). At the same time,Beclin 1 was decreased after injury with lowest expression on day 7(P＜0.05). The BBB scores of BPS group were increased with a dose-dependent manner as compared with SCI group. The cavity of dorsal white matter and central gray matter shrinked. The number of neurons was increased with intact morphology. The expression of Beclin 1 and LC3 Ⅱ/Ⅰ was increased significantly in BPS group, while p62 decreased as compared to SCI group(P＜0.05). Conclusions BPS has a well-demonstrated neuron-protective effect and the underlying mechanism might be related to the protection of injured nerve cells.

Objective To explore the potential anti-depression effect of the screened nucleic acid aptamers via blocking 5-HT re-uptake binding to the 5-HTR. Methods The mouse gene coding 5-HT_1AR was cloned, constructed, and the recombinant 5-HT_1AR was expressed and purified. The ssDNA aptamer that binds 5-HT_1AR specifically was screened by SELEX. The binding sites and binding affinity of ssDNA were measured. At the same time, ssDNA aptamer inhibitory protein uptake and the effect against depression were verified at cellular level and mouse depression model. Results The pET28a-5-HT_1AR plasmid was successfully cloned and constructed. The pET28a-5-HT_1AR protein was purified by 6× His label after transfected into E.coli DH5ɑ. The protein was consistent with mouse 5-HT_1AR by peptide fingerprint analysis. After 12 rounds of positive screening and 5 rounds of negative screening, four aptamers with high affinity and high specificity were obtained and the same epitope was bounded by four aptamers shown by results of enzyme-linked oligonucleotide assay(ELONA).The 5-HT uptake was influenced by aptamer 18 in vitro, and the improvement of depression state after intravenous injection of aptamer 18 was proved by the tail suspension experiment in mice. Conclusions Aptamer for 5-HTR is expected to be a new type of antidepressant used in the treatment of clinical depression. And this research also might provide a novel tool for screening of small molecule antagonist.

Objective To explore the effects of silencing endothelial PAS domain-containing protein 1 (EPAS1) on the proliferation, migration and invasion of human renal clear cell carcinoma cell line HiMet-ccRCC and to discuss the possible mechanism. Methods HiMet-ccRCC cells were divided into control (Con) group, negative control (NC) group and silencing EPAS1 expression group (EPAS1 siRNA group). RT-qPCR was used to detect the EPAS1 mRNA level in HiMet-ccRCC cells; MTT method was used to detect the proliferation of HiMet-ccRCC cells; Transwell experiment was used to detect the migration and invasion ability of HiMet-ccRCC cells; Western blot was used to detect the expression of E-cadherin,N-cadherin,MMP-9,PCNA. Results Compared with Con and NC group, the expression level of EPAS1 in HiMet-ccRCC cells in the EPAS1 siRNA group was significantly reduced (P＜0.05), the proliferation inhibition rate of HiMet-ccRCC cells was significantly increased and the counting of invasion and migration cells was significantly reduced (P＜0.05), the protein expression of E-cadherin in HiMet-ccRCC cells from EPAS1 siRNA group increased (P＜0.05)and the protein expression of N-cadherin, MMP-9 and PCNA reduced(P＜0.05). Conclusions Silencing EPAS1 could inhibit the proliferation, migration and invasion of HiMet-ccRCC cells and EPAS1 may be a potential biological target for gene therapy of renal clear cell carcinoma.

Objective To investigate the expression of Notch-1 in peripheral blood monocytes in patients with hypertensive retinopathy (HRP) and the possible relationship with vascular endothelial function. Methods Forty-two HRP patients were selected as HRP group and 30 healthy peoples were selected as control group. Peripheral blood serum and monocytes were collected. The levels of Notch1 mRNA and protein were determined by RT-PCR and Western blot, respectively. The level of VEGF, IGF-1, ET-1 and NO in serum was determined. Results The level of Notch1 mRNA and protein in HRP group was significantly lower than those in control group(P＜0.01,P＜0.05), especially in stage Ⅲ and Ⅳ(P＜0.01,P＜0.05). The levels of VEGF, IGF-1 and ET-1 in HRP group were significantly higher than those in control(P＜0.05) and NO was significantly lower than that in control(P＜0.05). The level of Notch1 was negatively correlated with VEGF, IGF-1 and ET-1(P＜0.05) and positively correlated with NO in patients with hypertensive retinopathy(P＜0.05). Low level of Notch1 was an independent risk factor for HRP (OR:0.733,95% CI:0.601-0.835,P＜0.001). Conclusions The level of Notch1 of peripheral blood monocytes is decreased in HRP patients, and vascular endothelial dysfunction may be associated with low level of Notch1.

Objective To investigate the effect of allicin on the reduction of learning ability and hippocampal neuronal apoptosis of obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. Methods The rats were divided into control group, model group, low-dose(10 mg/kg) and high-dose(40 mg/kg) of allicin group as well as positive drug group (modafinil, 20 mg/kg) with 18 in each. Morris water maze method was used to evaluate the learning ability of rats. HE and TUNEL staining microscopy was used to observe hippocampal tissue lesions and neuron apoptosis index (AI). ELISA method was used to detect tumor necrosis factor(TNF-α) and interleukin-6(IL-6) and advanced glycation end products (AGEs)in hippocampal tissue. RT-qPCR was used to detect advanced glycosylation end product-specific receptor (RAGE), nuclear transcription factor κB(NF-κB) p65, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein(Bax) mRNA expression. Western blot was used to detect RAGE, NF-κB p65, p-NF-κB p65, Bcl-2 and Bax protein. Results Compared with the control group, the escape latency was longer, travel time was shorter, cross-platform times was reduced. The expressions of TNF-α, IL-6, AGEs, AI, RAGE, Bax mRNA and RAGE, p-NF-κB p65, Bax protein were increased while Bcl-2 mRNA and protein expression decreased in the model group(P＜0.05). Compared with the model group, the above changes in the low-dose, high-dose allcin and positive drug group were significantly alleviated. HE results showed that the damage of hippocampal neurons in each treatment group was significantly mitigated. Conclusions Allicin can effectively improve learning ability and reduce apoptosis of hippocampal neurons in OSAHS rats, which may play a role through AGEs-RAGE/NF-κB axis and apoptosis-related mRNA and protein expression.

Objective To compare the efficacy and adverse reactions of esophageal cancer patients treated with different radiotherapy doses and concurrent chemotherapy. Methods The subjects of this study were esophageal cancer patients receiving radiotherapy and chemotherapy in Taihe County People's Hospital from March 2020 to March 2022. A total of 40 patients were enrolled and divided into control group (high-dose group, n=20) and experimental group (low-dose group, n=20) by random number table method. The efficacy, adverse reactions and prognosis of the two groups were compared and analyzed. Results After low-dose radiotherapy and chemotherapy, the clinical efficacy of the experimental group was slightly higher than that of the control group, but the difference was not significant. There was no significant difference in SF-36 score and KPS score between the two groups. The total incidence of adverse reaction in experimental group was lower than that in control group(P＜0.05). Conclusions Radiotherapy combined with chemotherapy has a good effect on patients with esophageal cancer and low dose radiotherapy has less adverse reactions and higher safety.

Objective To investigate the effects of lncRNA-ATB on the proliferation and collagen synthesis of human keloid fibroblast (KFB) and its possible molecular mechanism. Methods Human KFB and normal fibroblasts (NFB) were isolated and cultured in vitro, KFB was divided into NC group, si-NC group, si-lncRNA-ATB group, si-lncRNA-ATB+TNF-α group. RT-qPCR was used to detect the expression of lncRNA-ATB in NFB and KFB. MTT was used to detect cell activity. Flow cytometry was used to detect cell cycle. Western blot was used to detect expression of cyclinD1, collagen synthesis and NF-κB signaling pathway related protein. Results The expression of lncRNA-ATB in KFB cells was significantly increased (P＜0.05). Knock-down lncRNA-ATB expression decreased the A value of KFB cells, the expression of cyclinD1 and the percentageof S phase cells,but increased the percent- age of G₀/G₁ phase cells (P＜0.05); the expression of Col-Ⅰ and Col-Ⅲ of collagen was decreased(P＜0.05); the expression of p-p65 and p-IκBα in NF-κB signaling pathway was inhibited(P＜0.05); NF-κB activation activator TNF-α alleviated the inhibitory effect of knock-down lncRNA-ATB expression on KFB cell proliferation and collagen synthesis (P＜0.05). Conclusions Knock-down of lncRNA-ATB expression may inhibit KFB proliferation and collagen synthesis by down-regulating NF-κB signaling pathway.

Objective To investigate the effect and potential mechanism of recombinant Newcastle disease virus rL-RVG on proliferation and migration of human small cell lung cancer cell line NCI-H446. Methods NCI-H446 cells were divided into 3 groups: incubated with PBS, Newcastle disease virus(NDV) and rL-RVG, respectively. Immunofluorescence assay was used to detect the expression of RVG and NDV protein. MTT assay was used to determine the anti-proliferation of the virus. The cell migration was detected by scratch test and Transwell method. Immuno-fluorescence assay was used to detect the expression of E-cadherin and MMP2 proteins. Results After infection, rL-RVG stably expressed in NCI-H446 cell with high infection efficiency.The scratch distance in rL-RVG group was significantly shorter than that in NDV group and control group(P＜0.05). In the Transwell experiment, the number of cells crossing the compartment in the rL-RVG group were significantly less than that in the control group(P＜0.05). MMP2 protein expression was down-regulated in rL-RVG group, while E-cadherin protein expression was up-regulated(P＜0.05), compared with NDV group and control group. Conclusions rL-RVG could inhibit the proliferation of NCI-H446 cell with the potential mechanism of effects on cell migration through regulating E-cadherin and MMP2.

Objective To investigate the effect of pseudolaric acid B (PAB) on apoptosis of prostate cancer cell line DU145 and the potential mechanism. Methods The cells were treated with 0, 5, 10, 20 and 40 μmol/L PAB for 24, 48, 72 and 96 hours respectively;the CCK8 method was used to detect cell proliferation,flow cytometry annexin V-FITC/PI double staining and TUNEL method was used to detect cell apoptosis after the treatment of PAB. Scratch test and transwell chamber were used to detect cell migration and invasion. Western blot was used to detect the protein expressions of Bcl-2, Bax, PTEN, AKT and p-AKT in the cells. Results With the increase of PAB concentration and time of incubation, the cell viability of DU145 cells was significantly reduced (P＜0.01). Compared with the control group, the average cell apoptosis rate, Bax and PTEN protein expression in the PAB group were significantly increased, while the cell scratch healing rate, the number of transmembrane cells, Bcl-2 and p-AKT protein expression were significantly reduced(P＜0.01). GW9662 significantly reversed the pro-apoptotic effect of PAB on DU145. Conclusions PAB may inhibit the proliferation and invasion of prostate cancer DU145 cells and induce cell apoptosis through the PTEN/AKT signaling pathway.

Objective To investigate the expression of erythropoietin-producing hepatocyte B2 (EphB2) receptor at different phases of functional recovery after middle cerebral artery occlusion(MCAO) in rats. Methods Sixty-four rats were divided into four groups:sham group and 2, 14 and 28 days after MCAO. The neurological and motor function was evaluated with a modified mNSS score at 2 d, 14 d or 28 d after surgery. The mRNA and protein in the hippocampus and cortex were measured by q-PCR and Western blot, respectively. Results Rats showed the highest mNSS score at 2 d after MCAO as compared with sham group (P＜0.001) and the score decreased with time.The protein level of EphB2 receptor in the hippocampus increased significantly at 2 d after MCAO (P＜0.05)compared with sham group, and then gradually decreased at 14 and 28 d after MCAO. The expression of EphB2 receptor showed correlation with mNSS scores. However, the expression of EphB2 receptors in the cortex and the EphB2 mRNA level in the hippocampus did not change significantly after MCAO. Conclusions The expression of EphB2 receptor in the hippocampus is up-regulated at early phase of MCAO and then decreased, which is closely correlated with functional score in rats.

Objective To investigate the expression and its significance of miR-21 and B-cell lymphoma-2(Bcl-2) protein in skin lesions of Xinjiang Uygur patients with psoriasis vulgaris. Methods The expressions of miR-21 were measured with real-time fluorescent quantitative PCR in the 15 psoriatic vulgaris lesions and beside-lesional tissue as well as 15 normal skin samples collected from patients in People's Hospital of Xinjiang Uygur Autonomous Region from 2013 to 2019. The expressions of Bcl-2 were measured with immunohistochemical method in the 51 Uygur patients with psoriasis vulgaris and 29 Uygur normal control. The positive mainly as brown or tan particles in cytoplasm. miR-21 mimics and inhibitors were transient transfected into HaCaT cells. The expression of Bcl-2 protein in transfected cells was detected by Western blot. Results With real-time fluorescent quantitative PCR, the expression of miR-21 was higher in lesions of psoriasis vulgaris than in the beside-lesional tissue(P＜0.01) and normal skin tissue(P＜0.05). Immunohistochemical results showed that the positive expression of Bcl-2 protein was located in the cytoplasm and membrane. The expression rate of psoriasis vulgaris was 35.29%, which was lower than that of normal skin tissue(93.10%)(P＜0.01).The expression of Bcl-2 protein in HaCaT cells transfected with miR-21 mimic and miR-21 inhibitor was detected. With overexpressing miR-21, the expression of Bcl-2 was decreased. With inhibiting miR-21 expression, the Bcl-2 expression was increased(P＜0.01). Conclusions Abnormal expression of miR-21 and Bcl-2 protein in the skin of Xinjiang Uygur patients with psoriasis vulgaris may be involved in the potential mechanism.

Objective To investigate the quality of patient participation in clinical decision-making and the decision preference of patients in the diagnosis and treatment of stable coronary artery disease(SCAD)and to analyze the influencing factors of decision quality. Methods A total of 126 inpatients in Fuwai Hospital were selected by convenience sampling to investigate their decision quality and decision preference. Univariate analysis and binary logistic regression were used to analyze the influencing factors of decision quality. Results Among 126 patients, 50(39.7%) were active, 26(20.6%) were shared and 50(39.7%) were not active. The average score of decision quality was 81.39. Univariate analysis showed that annual household income, treatment satisfaction and decision preference were the influencing factors of decision quality (P＜0.05). Logistic regression analysis showed that patients with high treatment satisfaction (OR=6.722, 95% CI:2.635-17.148) and shared decision preference (OR=5.152, 95% CI:1.477-17.975) had higher decision quality. Conclusions In the diagnosis and treatment of SCAD, shared decision preference can improve decision quality and improve satisfaction. The characteristics of patients are not related to decision quality. To improve the decision quality needs to start with doctors and hospital.

Objective To explore epidemiological and clinical characteristics of corona virus disease 2019(COVID-19) in southern Liaoning Province aiming for its pathogenesis and providing evidence to support and optimize the diagnosis, treatment and prevention. Methods A retrospective analysis was performed by collecting the case information, case history and clinical indicators in 24 hours of admission including asymptomatic and mild/moderate type confirmed cases from February 2020 to January 2021 in southern Liaoning Province. The epidemiological characteristics were studied by descriptive analysis.The clinical characteristics of asymptomatic infection group and mild/moderate infection group were compared by t test, Mann-Whitney U test or pearson χ² test. The differential indexes were included in the binary Logistic regression model for further analysis. Results In 218 cases of COVID-19, 59 were asymptomatic(27.06%) and 159 were mild/moderate(72.94%). The ratio of males to females was 0.79∶1.00. Among all the patients,155 cases(71.10%) aged 31-60 years old, 78 cases(35.78%) were workers and 212 cases(97.25%) were located in Dalian. There were significant differences in age, length of hospital stay, platelet(PLT), lactic dehydrogenase(LDH), total protein(TP), albumin (ALB), blood uric acid (BUA) and c-reactive protein (CRP) between the two groups. The logistic regression model showed that age, LDH and CRP were the risk factors of clinical symptoms after virus infection (P＜0.05). Conclusions In southern Liaoning Province most of COVID-19 cases are mild/moderate. The majority of patients come from Dalian and the main age distribution is 31-60 years old. In terms of clinical diagnosis and treatment, it is suggested that LDH and CRP should be examined as soon as possible for older risk population, that may support early prediction of the disease progress and take more effective prevention and control measures.

Melanosome (MS) is a special membrane organelle which synthesizes, stores and transports melanin in melanocytes (MC). The diversity of human skin color lies on the type, quantity, distribution and maturation of MS. The transport of MS in MC is the result of the interaction between three kinesins and two kinds of cytoskeletons, which are affected by many regulatory factors. A variety of pigmented diseases are strongly associated with MS transport malfunction. A deeper understanding of the mechanism for MS transport may improve the cognition of MS transport-related diseases and potentially provide a novel strategy for clinical treatment and pharmaceutical development.

Circular RNA is a kind of RNA molecule with special covalent closed circular structure. The existing research results showed that circular RNA zinc finger RNA binding protein (circRNA-ZFR) was abnormally expressed in many malignant tumors, and its expression level was closely related to tumor clinical stage, cell metastasis and patient prognosis. circRNA-ZFR could participate in the regulation of tumor occurrence and development through endogenous competitive adsorption of miRNA, regulation of cell cycle and activation of multiple signal pathways. Further study on the expression and mechanisms of circRNA-ZFR in malignant tumors may support early diagnosis, targeted therapy of related tumors and patients' prognosis.

Human fat mass and obesity associated protein FTO is the first confirmed N⁶-methyladenosine(m6A) demethylase, which demonstrated the existence of reversible RNA modification, and also unveiled the prelude of m6A modification research. More and more researchers have tried to explore the specific mechanism of gene expression regulation at the level of m6A modification. It is found that m6A modification function requires the joint participation of methylesterase, demethylase, and binding protein to complete. FTO catalyze the demethylation of m6A modifications on mRNAs and is widely expressed in human tissues and participate in the regulation of various biological processes. This paper outlines the relationship between demethylase FTO and its mediated m6A/RNA modification and the development of body fat tissue, embryonic tissue, brain and neuro-system, hoping to gain insight into the function and mechanism of FTO.

Mycobacterium tuberculosis(M.tuberculosis, Mtb)is the causative agent of tuberculosis and can survive through regulating intracellular phagocytosis and affect the biological function of host cells. Rab proteins are important components of intracellular membrane transport and involved in the phagocytosis of Mtb. This review summarized the effect of Mtb and its compositions on intracellular phagocytosis and the role of Rab in this process. Thus this review may provide some ideas to understand the relationship between Rab proteins and the phagocytosis of Mtb, and to provide new thoughts and potential targets based on exploring the intracellular immune mechanism of Mtb.

Kisspeptin activates the hypothalamic-pituitary-gonadal axis (HPGA) and regulates the pulsatile secretion of gonadotropin-releasing hormone (GnRH) through KNDy neurons, thereby regulating the initiation of the pubertal phase. This review focuses on the mechanism of GnRH regulation by Kisspeptin and the role of Kisspeptin in the hypothalamic, pituitary and ovarian, aiming to provide reference for clinical management of abnormal pubertal development.

Bladder outlet obstruction (BOO) increases micturition resistance and prolongs the duration of intravesical hypertension. The intravesical pressure overloads the hydrostatic pressure and mechanical tensile force of detrusor,which triggers the cascade reaction of muscle cells starting from mechanical tension stress, hypoxia and ischemia-reperfusion injury (IRI), leading to changes in intracellular metabolism and reconstruction of extracellular matrix.The change of interstitial components is irreversible injury, and there is no effective treatment measures in the decompensation stage. At present, the exact pathogenesis is not completely clear. The study on the pathogenesis of BOO may support early detection of obstructive dysuria, which is of great significance for clinical treatment.

Raynaud's phenomenon is a common vasospasm response, and current medical therapies and surgical treatments show limited clinical effects. Botulinum toxin type A has certain effectiveness and safety in treating Raynaud's phenomenon. It can relax blood vessels, relieve pain, and has a good long-term effect. Its side effects are mild, such as pain at the injection site, bruises, or transient muscle weakness. In recent years, some research has broadened the scope of application of the treatment and determined more effective injection doses and injection methods to reduce the side effects. More large-sample randomized double-blind controlled trials and animal experiments are needed to provide information for explaining the treatment mechanisms and illstrating the efficacy.

Colon rectal neoplasia differentially expressed (CRNDE) RNA is a long non-coding RNA molecule that regulates gene expression at multiple levels including transcriptional, post-transcriptional and translational levels, plays a role in a variety of physiological and pathological processes. CRNDE is involved in the development and prognosis of colorectal tumors, glioma, hepatocellular carcinoma and other tumor diseases, inflammatory response such as pneumonia and sepsis, diabetic cardiomyopathy and osteoporosis. So it is expected to be a new biomarker or therapeutic target.

The training of clinical operational skill is an important part of medical education. Direct observation of procedural skills (DOPS) is a method to evaluate clinical operational skills. It has both teaching and evaluation functions. The evaluator directly observes the operation process of the evaluated and gives evaluation and feedback in time. This paper introduces the reliability, validity, feasibility, acceptability and educational significance and the current application of DOPS.

Research integrity is the basic norm of scientific activities. This article introduced the current situation of neurosurgery postgraduates in doing scientific research and delineated the hidden dangers of academic misconduct in the academic environment of neurosurgery. Furthermore, we emphasized the means to build and strengthen research integrity. The intention of this article is to, for the postgraduate population of neurosurgery, prevents academic misconduct, strengthen the construction of research integrity, and promote the development of neurosurgery discipline.

Objective To evaluate the application of online-teaching in ultrasound-guided regional block. Methods A total of 356 students (September 2020 to October 2020) who participated in three-phase online teaching in ultrasound-guided regional block were enrolled. Questionnaire regarding the online teaching were distributed to gather the feedback opinions. Results 81.47% of the students responded positively about online-teaching. 71.63% of the students agreed that online-teaching didn't impact their learning experience. 63.82% of the students thought the interactivity of online teaching was satisfying. 59.41% of the students preferred online-teaching to traditional teaching in ultrasound-guided regional block. Conclusions The online-teaching in ultrasound-guided regional block is accepted well by trainers. Further combination of online-teaching and hands-on workshop training may improve the teaching quality by complementary mutual advantages.

Clinical teaching round is an important way to train students' clinical capacity. Standardized patient (SP) can simulate real clinical situations accurately and reproducibly. Compared with the traditional teaching round, the teaching round with introduction of standardized patients has its unique advantages and can improve the standardization, homogeneity and generalization of clinical teaching rounds more effectively. This article introduces the current status of the application of standardized patients, its application in clinical teaching rounds and challenges, emphasizing its potential in clinical training.