Objective To investigate the correlation between rs368698783 and rs7482144 locus and fetal hemoglobin (HbF) expression in β-thalassemia patients of Yunan province. Methods A total of 579 samples were collected, including 51 samples of β-thalassaemia, 40 samples with HbE, 113 samples of HbF＞5%(β^N/β^N), 113 samples of HbF＞5%(β^M/β^N) and 262 samples from controls. Sanger sequencing was used to determine the genotypes of rs368698783 and rs7482144. The relationship between rs368698783 and HbF levels was analysed by comparing haematological parameters, mutant gene detection rates and MAF. Results The detection rate and MAF of mutated genes at the rs368698783 and rs7482144 loci were significantly higher in non-transfusion-dependent β-thalassaemia patients than that in controls(P＜0.05). The detection rate and MAF of mutated genes at the rs368698783 and rs7482144 loci were significantly higher in HbE pure samples than that in controls (P＜0.001). The detection rates of mutated genes and MAF at rs368698783 and rs7482144 loci were significantly higher in HbF＞5% (β^N/β^N) and HbF＞5% (β^M/β^N) samples than in the control group (P＜0.001). Conclusions The rs368698783 and rs7482144 mutation is associated with elevated HbF level and with HbE mutations. The A allele and T allele can reduce the degree of anaemia and alleviate the clinical symptoms of β-thalassemia.

Objective To investigate the effect of α-synuclein (α-syn) A53T mutant on mitochondria associated membrane (MAM) of endoplasmic reticulum, and to explore the molecular and cellular mechanism of neuronal toxicity induced by α-syn mutation. Methods Human neuroblastoma cell line SH-SY5Y with over expressed α-syn/A53T mutation gene, was constructed. MAM was labeled by proximity ligation assay and the number of MAM was counted. Mitochondrial calcium ions were labeled with Rhod2 and the changes of mitochondrial calcium ions were dynamically observed. The structure of mitochondria was further observed by laser confocal microscopy and electron microscopy. Results Over-expression of α-syn/A53T mutants resulted in significant cytotoxicity, inhibition of MAM calcium transport, and short rod-shaped and globular mitochondria as found by confocal laser microscopy. Mitochondrial vacuoles and autophagy were observed by electron microscopy. Conclusions α -syn/A53T mutants can cause mitochondrial structural abnormalities and autophagy by destroying MAM.

Objective To study the mechanism of learning and memory impairment in aged female mice caused by chronic stress. Methods Twenty-month-old ICR mice were randomly divided into four groups: control females, control males, stressed females, and stressed males. Chronic stress was applied to the stress group for 30 days. The learning and memory ability was measured by novel object recognition test and Morris water maze test. Damage to hippocampal neurons was observed with Nissl staining, and dendrites of hippocampal neurons were observed with Golgi-Cox staining microscopy, the expression of the mammalian target of rapamycin (mTOR) and p-mTOR in hippocampal tissue was measured by Western blot, and the level of serum corticotropin-releasing hormone (CRH) was measured by ELISA. Results There was a significant decrease in the learning and memory ability only in the stressed female group after applied stress. In the Morris water maze, after a 6-day swimming training, the escape latency decreased in the control female group, the control male group and in the stressed male group(P＜0.001, P＜0.001, P＜0.05), but not in the stressed female group. The swimming speed was consistent across groups, but the number of platform crossings and the number of target quadrant crossings were significantly lower in the stressed female group than those in the control female and stressed male groups(P＜0.001).There was significant damage to neurons in the hippocampal CA3, CA1, and DG regions of mice in the stressed female group. The expression of hippocampal m-TOR and p-mTOR protein was significantly decreased in the stressed female group of mice(P＜0.05). In addition, chronic stress caused a significant increase in serum CRH levels in aged female mice(P＜0.05). Conclusions Chronic stress caused learning and memory impairment and pathological damage of the hippocampus in aged female mice, but not in aged male mice, which may be related to a fact that chronic stress elevates CRH and inhibits the hippocampal m-TOR signaling pathway in aged female mice.

Objective To investigate the effect of radiation-induced bystander effect on donor bone marrow cells during bone marrow transplantation and the protective effect of aryl hydrocarbon receptor (AHR) inhibitor CH223191 on donor bone marrow cells. Methods The mice were divided into 9 Gy irradiated group and 12 Gy irradiated group. The same number of donor bone marrow cells were transplanted after different radiation doses. The total number of peripheral blood cells, chimerism rate and number of peripheral blood donor cells were detected by flow cytometry. Serum reactive oxygen species (ROS) level of unirradiated mice and irradiated mice were detected by ELISA. The donor bone marrow cells were divided into control group, 9 Gy irradiated group and 12 Gy irradiated group and were cultured in vitro. Unirradiated mouse serum, 9 Gy and 12 Gy irradiated mouse serum were added for treatment, respectively. ATP activity assay was used to detect cell vitality, and flow cytometry was used to detect cell apoptosis. The mRNA expression of Cyp1a1 and Cyp1b1 was detected by RT-qPCR. Bone marrow cells treated with irradiated serum were divided into CH223191 treatment group and control group. After adding CH223191 treatment, cell viability, cell apoptosis and intracellular ROS levels were compared, and mRNA expression of Cyp1a1 and Cyp1b1 was detected by RT-qPCR. Bone marrow transplantation mice were divided into CH223191 treatment group and control group. In the treatment group, CH223191 was injected intraperitoneally. The body weight, chimerism rate and number of peripheral blood donor cells, chimerism rate and number of donor cells in bone marrow were recorded. Results The total number of peripheral blood cells in the 12 Gy irradiated group was less than that in the 9 Gy irradiated group (P＜0.05), whereas there was no significant difference in the chimeric rate of peripheral blood donor cells after bone marrow transplantation. However, the number of peripheral blood donor cells in the 12 Gy irradiated group was significantly less than that in the 9Gy irradiated group (P＜0.05).The serum ROS level increased after irradiation (P＜0.01). The activity of donor bone marrow cells was decreased and the percentage of apoptosis was increased (all P＜0.01), and the mRNA of Cyp1a1 and Cyp1b1 were increased in irradiated mouse serum (P＜0.05). After CH223191 was added into donor bone marrow cells treated with irradiated mouse serum, the mRNA levels of Cyp1a1 and Cyp1b1 were decreased (P＜0.05), the cell viability was increased, the intracellular ROS level was decreased, and the percentage of cell apoptosis was decreased (all P＜0.01). After bone marrow transplantation, mice in CH223191 treatment group lost less body weight compared with control group, the chimeric rate and cell number of peripheral blood donor cells were higher than control group, and the proportion and number of donor cells in bone marrow were higher than control group (all P＜0.05). The total counting of peripheral blood cells in the 12 Gy irradiated group was less than that in the 9 Gy irradiated group (P＜0.05), whereas there was no significant difference in the chimeric rates. Conclusions CH223191 inhibits the activation of AHR, reduces the damage of radiation-induced bystander effect on transplanted bone marrow cells, and improves the effect of bone marrow transplantation in mice.

Objective To investigate the effect of miR-200c-5p on malignant proliferation of human colorectal cancer cell line SW480. Methods Human colorectal cancer cell line SW480 was transfected with miR-200c-5p mimic/inhibitor and negative control agent respectively. The expression of miR-200c-5p was detected by qPCR, and the effects of miR-200c-5p on the proliferation activity and clonogenesis ability of colorectal cancer cells were detected by CCK-8 and foci formation experiment. Bioinformatics methods were used to analyze the differential target genes and related pathways of miR-200c-5p in human colorectal cancer. Results Transient transfection with miR-200c-5p mimic/inhibitor succeeded in high/low expression of miR-200c-5p (P＜0.05). The proliferation of cells with high expression of miR-200c-5p was significantly inhibited as compare to that of controls(P＜0.05). The clone-formation rate of miR-200c-5p cells with high expression was significantly lower than that of untransfected cells, while the clone-formation rate of miR-200c-5p cells with low expression was the opposite (P＜0.05). CXCL10, the target gene of miR-200c-5p, was significantly up-regulated in colorectal cancer, while C2orf72, ZC3H12C and DST were significantly down-regulated. The most significant KEGG pathways were “melanoma”, “microRNAs in cancer” and “bladder cancer”. Conclusions miR-200c-5p inhibits the proliferation and clonal formation of human colorectal cancer cell line SW480, which is related to the occurrence and progression of colorectal cancer.

Objective To investigate the role of BEND6 in regulating gene expression in mouse neural stem cells (NSCs) and to explore its biological function during neural development. Methods pCMV-mScarlet (control group) and pCMV-mScarlet-BEND6 (experimental group) plasmids were transiently transfected into mouse NSCs, respectively. After 24 hours, the expression of mScarlet and mScarlet-BEND6 proteins was confirmed by the presence of red fluorescence. Total RNA was then extracted from the two groups of cells for RNA-seq. Through reference genome alignment, quantitative analysis, differential gene expression analysis and enrichment analysis of the sequencing data, we were able to profile the transcriptome of NSCs upon BEND6 overexpression and to suggest a function for mouse neural development. Results Mouse NSCs were successfully isolated for primary culture. Whole transcriptome sequencing analysis revealed 165 differentially expressed genes after force-expressing BEND6, among which 102 genes were up-regulated and 63 genes were down-regulated. Enrichment analysis showed that these differentially expressed genes were highly related to the regulation of membrane potential change, synaptic transmission, stimulation response, growth and development and other biological processes. Conclusions BEND6 regulates the expression of genes related to neuronal functions in mouse NSCs, which suggests a potential mechanism in regulating neuron specific biological processes during development.

Objective To investigate the impact of midazolam on hypoxia-reoxygenation-induced neuronal injury based on mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathway. Methods Mouse hippocampus neurons were cultured in vitro and the effects of 0, 5, 10, 40, 70 and 100 ng/mL midazolam on cell viability after hypoxia and reoxygenation were detected by MTT assay, and the best concentration was screened out. The cultured mouse hippocampus neurons were randomly separated into control group, model group (anoxic for 3 hours and reoxygenated for 12 hours), midazolam (70 ng/mL) group, C16-PAF (MAPK activator, 4 μmol/L) group, and midazolam (70 ng/mL) + C16-PAF group (4 μmol/L). The apoptosis of neurons was detected by Hoechst33258 staining and flow cytometry; the releases of lactate dehydrogenase (LDH), tumor necrosis factor-α(TNF-α), interleukin-18 (IL-18), and interleukin-17 (IL-17) and the levels of cellular superoxide dismutase (SOD) and catalase (CAT) were detected by ELISA; the expression of apoptosis proteins and MAPK/NF-κB pathway proteins were detected by western blotting. Results Compared with the control group, the neuron apoptosis rate, LDH, the TNF-α, IL-18, IL-17 releases, apoptosis protein caspase-9, Bax expression, and MAPK/NF-κB pathway p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 levels were significantly increased in the model group (P＜0.05), the CAT and SOD levels in cells were significantly decreased (P＜0.05). Compared with the model group and midazolam+C16-PAF group, the neuron apoptosis rate, LDH, the TNF-α, IL-18, IL-17 releases, apoptosis protein caspase-9, Bax expression, and MAPK/NF-κB pathway p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 levels were significantly decreased in the midazolam group (P＜0.05), the CAT and SOD activity in cells were significantly increased (P＜0.05); the neuron apoptosis rate, LDH, the TNF-α, IL-18, IL-17 releases, apoptosis protein caspase-9, Bax expression, and MAPK/NF-κB pathway p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 levels were significantly increased in the C16-PAF group(P＜0.05), the CAT and SOD levels in cells were significantly decreased (P＜0.05). Conclusions Midazolam can reduce the expression of inflammatory cytokines by inhibiting the activation of MAPK/NF-κB signaling, thereby inhibiting the inflammatory and oxidative stress responses induced by hypoxia and reoxygenation, reducing neuronal cell damage and its apoptosis rate.

Objective To analyze the clinical features and to identify the pathogenic variants in three Chinese families with dyschromatosis symmetrica hereditaria (DSH). Methods Clinical information and peripheral blood samples from three trio families with DSH were collected. The variants were detected by whole exome sequencing and then confirmed by Sanger sequencing. Pathogenicity of the variants was evaluated with a series of bioinformatic software. Results All the probands from the three Chinese families showed a mixture of pigmented and depigmented macules on the extremities. Three heterozygote single-nucleotide-variants, c.3546T＞G (p.Tyr1182*), c.2770T＞G (p.Tyr924Asp) and c.3116A＞C (p.Lys1039Thr), in the ADAR(NM_001111.5) gene were detected by WES in the three probands respectively. The first two variants were not present in the public databases such as gnomAD and HGMD, and the third one was previously reported in HGMD but not presented in the public databases. The relevant variants were undetectable in their parents of the three probands shown by Sanger sequencing, and were consequently regarded as de novo variants. These variants located in the highly conservative sites, all of which were located in the double-stranded RNA adenosine deaminase domain of the protein encoded by ADAR. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the nonsense variant, c.3546T＞G in ADAR, was categorized as a pathogenic variant (PVS1+PS2+PM2+PP3+PP4) and the missense variants, c.2770T＞G and c.3116A＞C in ADAR, were categorized as pathogenic variants (PS2+PM1+PM2+PP3+PP4) and (PS1+PS2+PM1+PM2+PP3+PP4), respectively. Conclusions Three de novo variants in ADAR, c.3546T＞G, c.2770T＞G and c.3116A＞C are probably the genetic pathogenesis of DSH in these three probands respectively, which enriched the genetic profile of ADAR.

Objective To investigate the effect of isorhamnetin on the apoptosis of retinal cells in diabetic retinopathy (DR) rats. Methods The rats were divided into control group, DR model group, low and high dose isorhamnetin groups (ISO-L group, ISO-H group, 50, 150 mg/kg isorhamnetin orally, respectively) and positive drug group (150 mg/kg calcium dobesilate orally). The level of serum inflammatory factors was measured by ELISA; HE staining and TUNEL staining were performed to observe the pathological changes and cell apoptosis of retina. Western blot method was performed to detect protein expression of VEGF, Bax, caspase-3 and phosphorylation levels of p38 MAPK, NF-κB p65 in retinal tissue. Results Compared with the control group, the retina of the model group was arranged disorderly, the boundary was unclear, the inner and outer nuclear layers were edema, the number of cells was reduced, and the thickness of the retina became thinner, and the retinal cell apoptosis rate, serum TNF-α, IL-1β, IL-6 levels, VEGF, Bax, caspase-3 protein expression and p38 MAPK, NF-κB p65 phosphorylation were significantly increased (P＜0.05); Compared with the model group, the retinal tissue layers of the ISO-L, ISO-H, and positive drug groups had clearer boundaries, slightly looser structures, and increased retinal thickness, and the retinal cell apoptosis rate, serum TNF-α, IL-1β, IL-6 levels, VEGF, Bax, caspase-3 protein expression, and p38 MAPK, NF-κB p65 phosphorylation levels were significantly reduced (P＜0.05). Conclusions Isorhamnetin may ameliorate retinal injury and cell apoptosis in DR rats by inhibiting the MAPK/NF-κB signaling pathway.

Objective To investigate the effect of miR-210 on hydrogen peroxide (H₂O₂)-induced adipogenic differentiation of rat bone marrow mesenchymal stem cells (BM-MSCs). Methods The SD rat BM-MSCs were isolated, cultured and identified. BM-MSCs were induced by 200 μmol/L H₂O₂ for 1 h to construct an adipogenic differentiation model. Adipogenic differentiation models were transfected with miR-210 mimic or inhibitor, respectively. RT-qPCR to detect the expression of miR-210; oil red O staining to detect the fat particles in the cytoplasm of cells; Western blot to detect the expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT enhancer binding protein (C/EBPa) and Wnt/β-catenin pathway related proteins of cells. Results SD rat BM-MSCs were successfully isolated. In adipogenic differentiation model of BM-MSCs, the levels of miR-210, β-catenin, c-Myc, and cyclin D1 protein decreased, while the number of fat granules, PPARγ and C/EBPα protein levels increased; In BM-MSCs transfected with miR-210 mimic, the levels of miR-210, β-catenin, c-Myc, and cyclin D1 protein increased, while the fat granules, PPARγ, and C/EBPα protein level all decreased; The change trend of corresponding indexes in BM-MSCs transfected with miR-210 inhibitor was opposite to that in BM-MSCs transfected with miR-210 mimic. Conclusions Over-expression of miR-210 could inhibit the adipogenic differentiation of BM-MSCs induced by H₂O₂. This mechanism may be related to the activation of Wnt/β-catenin pathway.

Objective To explore potential mechanisms involved in the reduction of podocyte apoptosis and oxidative stress induced by high glucose (HG) by tanshinone ⅡA (Tan ⅡA). Methods CCK-8 method was used to screen the appropriate interference concentration of Tan ⅡA. The MPC-5 cells were divided into NC group (5.5 mmol/L D-glucose), MA group(5.5 mmol/L D-glucose and 22.5 mmol/L mannitol), HG group(25 mmol/L D-glucose), HG+Tan ⅡA group(25 mmol/L D-glucose and 10 μmol/L Tan ⅡA), and HG+Tan ⅡA+SIRT1 inhibitors(sirtinol) group (25 mmol/L D-glucose, 10 μmol/L Tan ⅡA and 20 μmol/L sirtinol). Determina- tion of oxidative stress markers malondialdehyde(MDA), superoxide dismutase (SOD) and catalase (CAT) were made by microplate method, WST-1 method and visible light method. Flow cytometry was used to measure cell apoptosis. Western blot was used to evaluate the expression of apoptosis-related proteins and silent information regulator 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway proteins. Results Tan ⅡA improved the viability of MPC-5 cells induced by HG (P＜0.05). Compared with the MA group, the level of cell apoptosis in the HG group increased, the expression of B-cell lymphoma-2 gene (Bcl-2), phosphorylated SIRT1 (p-SIRT1) and phosphorylated eNOS(p-eNOS) in the cells, and the activity of SOD and of CAT were reduced, the expression of Bcl-2-associated X protein (Bax) and cleaved caspase-3, and the content of MDA in cells were increased(P＜0.05). Compared with the HG group, the level of cell apoptosis in the Tan ⅡA group reduced, the expressions of Bcl-2, p-SIRT1 and p-eNOS in the cells, and the activity of SOD and CAT were increased, the expression of Bax and cleaved caspase-3, and the content of MDA in cells were reduced(P＜0.05). The SIRT1 inhibitor sirtinol attenuated the inhibitory effect of Tan ⅡA on HG-induced podocyte apoptosis and oxidative stress (P＜0.05). Conclusions Tan ⅡA may reduce HG-induced apoptosis and oxidative stress in podocytes with a potential mechanism of activating the SIRT1/eNOS pathway.

Objective To investigate the effects and mechanism of metformin(Met) on the proliferation of cervical squamous cell carcinoma. Methods CCK-8 method was used to check the proliferation of cells lines SiHa and CaSKi, the semi inhibitory concentration of metformin (IC₅₀) was calculated as well.The cell cycle and apoptosis were examined by flow cytometry, and the expression of AMPK-mTOR signal pathway related proteins was detected by Western blot. Results With the increase of drug concentration and time, the cell proliferation rate decreased(P＜0.05).The IC₅₀ concentrations of SiHa cells at 48 and 72 h were (50.95±2.63) and (21.39±5.23) mmol/L respectively, and those of CaSki cells were (9.98±1.63) and (7.47±2.09)mmol/L, resepectively. The content of G₂/M phase cells decreased and S phase cells increased in Met group (P＜ 0.05). The apoptosis rate of Met group was higher than that of control group (P＜ 0.05). The expression of p-AMPK in the Met group was higher than that in the control group, while p-S6K and p-4E-BP1 were lower(P＜ 0.05). Conclusions The inhibitory effect of metformin on the proliferation of cervical squamous cell carcinoma lines may be related to the mechanism of promoting apoptosis,blocking cell cycle at S phase and activation of AMPK-mTOR signal pathway.

Objective To explore potential correlation between liver inflammatory response and viral infection index in patients with hepatitis B virus(HBV). Methods Totally 198 serum samples from HBV infected patients and healthy subjects were collected. Patients were divided into different groups according to alanine transaminase/aspartate transaminase(ALT/AST), HBV-DNA, hepatitis B E Antigen(HBeAg) and liver cirrhosis situation; ELISA was used to determine the B cell-attracting chemokine 1(BCA-1) and stem cell factor(SCF) level; the relationship between BCA-1, SCF and other clinical indicators, including ALT/AST, HBV-DNA, HBeAg and cirrhosis condition, were analyzed in different groups; the data was analyzed either with unpaired t test, or with Mann-Whitney U test according to normal distribution, and Spearman method was used for correlation analysis. Results The levels of serum BCA-1 and SCF in HBV infected patients were significantly higher than those in healthy controls(P＜0.001). The serum SCF level was significantly higher in cirrhosis patients than patients without cirrhosis(P＜0.01). The BCA-1 level was significantly different between HBV-DNA+ and HBV-patients, as well as between alpha-fetoprotein(AFP) normal and abnormal patients(P＜0.05). BCA-1 was significantly higher in HBV-DNA+ patients than that in HBV-DNA-patients and was lower in AFP abnormal patients than in normal patients. Furthermore, BCA-1 was positively relate to HBV-DNA and HBeAg level(R=0.314, R=0.456,P＜0.01). Conclusions BCA-1 was significantly related to HBV DNA, while SCF is upregulated in cirrhosis patients with HBV infection, which may be the potential candidate of clinical indicators for HBV infection.

Objective To investigate the relationship between the expression of CXC chemokine ligand 8 (CXCL8) and miR-150 in the skin lesions of patients with psoriasis vulgaris and the severity of the disease. Methods The skin lesions of 80 patients with psoriasis vulgaris who were treated in Nanyang first people's Hospital from January 2020 to May 2021 were selected as the research objects. The normal tissues around the skin lesion were chosen as a control. The Psoriasis Area and Severity Index (PASI) was used to classify patients with psoriasis, the immunohistochemical method was used to detect the expression of CXCL8 protein, the real time fluorescence quantitative PCR method was used to detect the expression of miR-150, Western blot was used to detect the expression of CXCL8 protein, and the correlation between the expression levels of CXCL8 protein, miR-150 and the severity of the disease was further analyzed. Results The level of CXCL8 mRNA in the skin lesion of patients with psoriasis vulgaris was higher than that in normal tissues (P＜0.05) and the level of miR-150 was lower than that in normal tissues(P＜0.05). The expression of CXCL8 protein in the skin lesions of patients was 68.75%, which was significantly higher than 37.50% in normal tissues (P＜0.05); the expression of CXCL8 protein in the skin lesions of patients was significantly higher than that in normal tissues (P＜0.05); the level of miR-150 gradually decreased with the aggravation of the disease (P＜0.05), and the level of CXCL8 protein gradually increased with the aggravation of the disease (P＜0.05); Pearson results showed that there was a negative correlation between miR-150 level in patients with psoriasis vulgaris and CXCL8 protein level and PASI score (r=-0.467, -0.475, P＜0.05), and there was a positive correlation between CXCL8 protein level and PASI score (r=0.424, P＜0.05). Conclusions The expression of miR-150 decreased and CXCL8 increased in patients with psoriasis vulgaris, both of them were related to the severity of the disease.

Objective To summarize the characteristics of patients with congenital solitary kidney(CSK). Methods Medical data and post-operative follow up results of patients that was diagnosed with congenital solitary kidney in Peking Union Medical College Hospital from 2012 to 2020 were collected. Results A total of 233 patients with congenital solitary kidney (58 males and 175 females) were included in this study.The most common deformity was genital tract deformity followed by congenital scoliosis.15% of CSK patients had other renal disease.Urological surgery was performed in 5 patients,and no postoperative complications occurred during follow-up. Only 1 patient presented recurrence and metastasis 1 year after partial nephrectomy and underwent secondary surgery. Conclusions When congenital solitary renal malformation is screened out, it is necessary to carry out systemic evaluation.As for surgical treatment,it should be carefully executed,and long-term follow-up should be conducted to monitor renal function.

Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells undergo morphological changes to gain a mesenchymal cell phenotype and migratory properties. As a class of negative regulators of RhoGTPases, RhoGTPase activating proteins(RhoGAP) can bridge between cell surface receptors and cellular actin cytoskeleton during EMT procedure, which may influence cancer cell transition and outcome of fibrotic diseases and may help search for anti-tumor and anti-fibrotic managements.

The relationship among oxidative stress, inflammations and stone formation has been proved. Mitochondria, as one of the most important organelles in cell, plays an important role in energy supply, oxidative stress, calcium homeostasis and cell programmed death. Mitochondrial dysfunction may accelerate the kidney stone-forming, which may be related to the decreased antioxidant capacity, the activation of inflammatory pathways, the imbalance of intracellular calcium and oxalic acid homeostasis. To clarify the roles of mitochondrial dysfunction in the formation of kidney stones may support the research on pathogenesis of the disease and to provide some potential novel ideas in the prophylactic study of renal stone in future.

Diabetic osteoporosis (DOP) is a common bone metabolic disease in patients with diabetes. Under the high glucose (HG) environment, abnormally expressed microRNA (miRNA) interferes with osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) by regulating key molecules in the Wnt/β-catenin signaling pathway, leading to the occurrence and development of DOP. Exploring the role of miRNA in DOP can provide new ideas for the diagnosis and treatment of DOP.

The diagnostic methods for colorectal cancer (CRC) are still improving. Liquid biopsy mainly analyzes the specific components of biological liquid. Long chain noncoding RNA (lncRNA) from exosomes can be analyzed by liquid biopsy technology.

Hyperuricemic nephropathy (HN) is a common clinical complication of hyperuricemia, leading to hyperuricemia-associated renal abnormalities. The present review sheds light on the mechanistic aspects pertaining to HN, emphasizing the role of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in the occurrence and development of HN.This review recommends pharmacological inhibition of NLRP3 infammasome as a therapeutic strategy of HN treatment.

Neovascular diseases involve multiple systems and organs and are a major category of diseases characterized by angiogenesis, including tumors, cardiovascular diseases and eye diseases. Microtubule inhibitors are a class of natural or synthetic drugs which inhibit neovascularization and block neovascularization through changing the state of microtubules. They may induce apoptosis and block cell cycle by affecting angiogenesis related genes and cytokines.

Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis(ALS). The mitochondrial dysfunction will cause severe oxidative stress and disruption in calcium homeostasis. The abnormally released mitochondrial DNA will induce cellular inflammation. These phenomena may explain the loss of motor neurons in ALS patients. As a quality control process, either abnormal increased or decreased mitophagy flux will speed up the pathogenic development of ALS.

Group A beta-hemolytic Streptococcus (GAS) is a common infectious agent in children which may cause recurrent inflammation of the tonsils, known as recurrent group A Streptococcus tonsillitis (GAS-RT). Recent studies found that GAS-RT is not an infectious disease as traditional sense, but rather than an immunosensitive disease that evades the immune response through the interaction between superantigens (SAgs) and follicular helper T cells (Tfh) in the germinal center (GC), which exerts a cytotoxic effects on B cells in the GC. This theory suggested a potential new strategy for clinical treatement.

Neutrophils are more innate immune cells found in coronavirus disease in 2019(COVID-19). The accounting of neutrophils and the level of plasma neutrophil extracellular traps(NETs) were positively correlated with the severity of COVID-19. This article reviews the relevant studies of neutrophils, formation and degradation of NETs involved in the pathological process of COVID-19, providing the reference for further studies of pathogenesis and intervention.

Objective To explore the application of a hybrid training mode characterized by “clinical practice + result oriented +humanistic care” for practical training of medical students. Methods The research objects were the graduate students at the department of ultrasound in Peking University Third Hospital, and the subjective evaluation index was the two-way questionnaire completed by teachers and by students. The recognition of teachers and students to the new training mode and its effectiveness as well as suggestions were evaluated. Results It was found that 95.74% of teachers and students acknowledged the new mode and were willing to participate in, 76.7% of them believed that the method helped to solve problems in work and psychology, 6.4% of teachers and students thought that the communication efficiency of new mode was lower than the traditional method. The advantages and disadvantages of the new model, the opportunities and threats of teaching and management were analyzed with SWOT. Conclusions The new hybrid traniniing model has got a high degree of recognition. According to the results of SWOT analysis, we should develop strengths and circumvent weaknesses, creating new opportunities for medical practice and educational model innovation.

Objective To explore the application effect of the flipped classroom with ideological-political in the molecular biology course. Methods A comparative study was conducted with undergraduates majored in clinical medicine from eight classes in grade 2019 as subjects, who were divided into control group using traditional teaching method containing ideological-political elements and the experimental group adopting the flipped classroom with ideological-political elements. Questionnaires, college students' self-learning ability assessment scale and an examination were used to evaluate the satisfaction of teaching mode, the improvement of students' self-learning ability and the teaching effects in the two groups. Results Compared with the control group, the performance of the students in the experiment group was statistically better than the control group (P＜0. 05) in terms of mastering the classroom knowledge, inspiring the interest in learning, enhancing the capacity of analysis and solving problems and teamwork, impoving class participation and guidance of ideological-political elements on future career planning. The self-learning ability of students in the experimental group was obviously improved. The theoretical test score of the experimental group was significantly higher than the control group (P＜0.05). Conclusions The application of flipped classroom with ideological-political elements in teaching molecular biology for the undergraduates can improve their performance skill and capacity building of self-learning.

Objective To evaluate the improvement effect of the modified three-step method(theoretical knowledge, basic skills, practical operation) applied in the training of laparoscopic skills of Eight-year Program of Clinical Medical students. Methods A total of 6 medical students in Peking Union Medical College who were in practice or just after practice and had no experience in laparoscopic operation were randomly selected as the experimental group for a period of 10 weeks, one time a week, 3 hours each time of modified three-step laparoscopic basic operation skills training and 6 medical students during the same period were trained by tradional method used as the control. The level of basic skill operation of medical students was evaluated at the beginning and at the end of the training in 10 items: basic clamping, advanced clamping, pile clamping, imitation meat suture, blunt separation, ultrasonic knife separation, ultrasonic knife cutting, simple intermittent suture, continuous suture, and lymphatic dissection. Results At the end of the training, students of experimental group performed better in 7 items of basic clamping, advanced clamping, pile clamping, imitation meat suture, ultrasonic knife separation, ultrasonic knife cutting and continuous suture. The operation time was significantly reduced or the score was significantly improved (P＜0.05). Conclusions The training of the improved three-step method can significantly improve the basic skills of laparoscopic operation of eight-year medical students, lay a solid foundation for the formal clinical operation and is an effective training method for medical students.

Ideological and political education is a process in which teachers of specialized courses integrate ideological and political education into classroom teaching and reform while imparting professional knowledge. It is the due meaning of medical education and the inevitable pursuit of medical colleges to carry out the fundamental task of cultivating people by virtue. How to integrate the ideological and political education into the teaching of medical professional knowledge needs teachers to play a leading role and to innovate the current teaching management mechanism. From the perspective view point of administrators, this paper puts forward some suggestions on how to improve the management mechanism and promote the development of ideological and political curriculum penetrating into all medical course.

Fixed assets are important resources of research work at basic medical research institutes. It is of practical significance to scientifically manage fixed assets, continuously improve their application efficiency, and minimize the loss and waste of assets for the orderly conduct of scientific research, teaching, and administrative work. This article takes the equipment assets of a basic medical research institute as an example and to analyze the weakness in the management of fixed assets of the institute, puts forward some new strategies to improve the management of fixed assets at basic medical research institutes.