OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases

Schizothorax argentatus that only distributes in the Ili River basin in Xinjiang is one of the rare and endangered species of schizothorax in China, thus has high scientific and economic values. In this study, the complete mitochondrial genome sequence of S. argenteus with a length of 16 580 bp was obtained by high-throughput sequencing. The gene compositions and arrangement were similar to those of typical vertebrates. It contained 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a non-coding region (D-loop). The nucleotide compositions were A (30.25%), G (17.28%), C (27.20%), and T (25.27%), respectively, showing obvious AT bias and anti-G bias. Among the tRNA genes, only tRNA-Ser^(GCU) could not form a typical cloverleaf structure due to the lack of dihydrouracil arm. The AT-skew and GC-skew values of the ND6 gene were fluctuating the most, suggesting that the gene may experience different selection and mutation pressures from other genes. The mitochondrial control region of S. argenteus contained three different domains, i.e., termination sequence region (ETAS), central conserved region (CSB-F, CSB-E, CSB-D, and CSB-B), and conserved sequence region (CSB1, CSB2, and CSB3). The conserved sequence fragment TT (AT) nGTG, which was ubiquitous in Cypriniformes, was identified at about 50 bp downstream CSB3. Phylogenetic relationships based on the complete mitochondrial genome sequence of 28 Schizothorax species showed that S. argenteus had differentiated earlier and had a distant relationship with other species, which may be closely related to the geographical location and the hydrological environment where it lives.
Animals ; Genome, Mitochondrial/genetics* ; Phylogeny ; Sequence Analysis, DNA ; Cyprinidae/genetics* ; RNA, Transfer/genetics* ; DNA, Mitochondrial/genetics* ; Genes, Mitochondrial

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective:To compare and analyze the clinical characteristics between acute fatty liver of pregnancy (AFLP) and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.Methods:This is a retrospective cohort study. The clinical data of 13 cases with AFLP and 34 cases with HELLP syndrome were collected from three tertiary referral centers in Yunnan (the First Affiliated Hospital of Kunming Medical University, the Second Affiliated Hospital of Kunming Medical University, and Yan'an Hospital of Kunming City) from January 2016 to December 2021. The patients were diagnosed to AFLP and HELLP syndrome according to the Swansea criteria and the Tennessee classification system. The general characteristics, clinical features, laboratory results within 24 hours after admission, complications, maternal and neonatal outcomes were compared to analysis the differences between the two groups.Results:① Maternal characteristics: compared with HELLP syndrome group, AFLP group had lower body mass index (BMI) and blood pressure at admission (both P < 0.01). ②Clinical features: the most common symptoms in AFLP patients were skin jaundice, abdominal pain, nausea and vomiting, edema. The main manifestations of patients with HELLP syndrome were albuminuria, hypertension, edema, headache. Some patients had multiple symptoms concurrently. ③ Laboratory results: compared with HELLP syndrome group, the levels of platelet count (PLT), total bilirubin (TBil), direct bilirubin (DBil), γ-glutamyl transferase (γ-GGT), alkaline phosphatase (ALP), total bile acid (TBA), serum creatinine (SCr) and international standardized ratio (INR) in AFLP group were significantly increased within 24 hours after admission [PLT (×10 9/L): 107.69±51.13 vs.76.71±43.25, TBil (μmol/L): 121.60 (83.20, 170.00) vs.15.25 (7.22, 29.05), DBil (μmol/L): 86.50 (58.60, 104.00) vs. 4.30 (2.22, 10.10), γ-GGT (U/L): 87.00 (37.00, 127.00) vs. 41.00 (19.00, 64.42), ALP (U/L): 199.10 (109.00, 349.20) vs. 125.50 (90.50, 155.25), TBA (μmol/L): 51.50 (16.20, 117.40) vs. 4.15 (2.02, 6.95), SCr (μmol/L): 155.80 (129.00, 237.00) vs. 79.00 (65.43, 113.70), INR: 1.28 (1.17, 1.63) vs. 0.94 (0.88, 1.08), all P < 0.05], prothrombin time (PT) was significantly prolonged [seconds: 16.10 (14.50, 19.20) vs. 12.40 (11.43, 13.40), P < 0.05]. The level of blood glucose (GLU), fibrinogen (FIB) and the activity of antithrombin Ⅲ (ATⅢ) decreased significantly [GLU (mmol/L): 5.18±1.33 vs. 6.33±1.19, FIB (g/L): 1.96±1.46 vs. 3.81±1.58, ATⅢ (%): 40.61±25.84 vs. 66.39±24.11, all P < 0.05]; ④ Complications: compared with HELLP syndrome group, the incidence of patients with hypoglycemia [30.77% (4/13) vs. 0% (0/34)], acute liver failure [53.85% (7/13) vs. 5.88% (2/34)], acute renal insufficiency [69.23% (9/13) vs. 8.82% (3/34)], coagulopathy [76.92% (10/13) vs. 38.24% (13/34)], disseminated intravascular coagulation (DIC) [53.85% (7/13) vs. 5.88% (2/34)], and multiple organ dysfunction syndrome (MODS) [53.85% (7/13) vs. 5.88% (2/34)] were significantly higher in AFLP group (all P < 0.05). ⑤ Maternal and neonatal outcome: all patients delivered after admission. The total length of hospital and intensive care unit stay were significantly longer in the AFLP group than in the HELLP syndrome group [days: 17.00 (11.00, 25.00) vs. 9.00 (7.00, 12.00), 12.00 (4.00, 22.00) vs. 3.91 (0, 7.00), both P < 0.01]. Two AFLP patients died, including one due to intracranial venous thrombosis and one due to multiple organ failure and cardiopulmonary arrest. There were no deaths in the HELLP syndrome group. Conclusions:There are significant differences in maternal characteristics, laboratory results and complications between AFLP and HELLP syndrome. TBil, γ-GGT, SCr, FIB, INR and ATⅢ activity may help to distinguish the two diseases.

Objective:To confirm items included in a tool for assessing clinical outcomes based on International Classification of Functioning, Disability and Health (ICF) Rehabilitation Set.Methods:The item pool was established based on the ICF Rehabilitation Set. Then 15 experts were invited to participate in three rounds of expert Delphi consensus-building to choose items with high importance in assessing clinical outcomes. The reliability of the tool was examined by analyzing the experts′ positive coefficients, authority coefficients and degree of agreement.Results:The assessment tool which emerged from the three rounds comprised 17 items, including 8 Body Functions items (b130 Energy and drive functions, b134 Sleep functions, b152 Emotional functions, b280 Sensation of pain, b455 Exercise tolerance functions, b620 Urination functions, b710 Mobility of joint functions and b730 Muscle power functions), d230 Carrying out daily routine from General Tasks and Demands, 3 Mobility items (d410 Changing basic body position, d450 Walking and d465 Moving around using equipment), 4 Self-care items (d510 Washing oneself, d530 Toileting, d540 Dressing and d550 Eating) and 1 item of Interpersonal Interactions and Relationships (d710 Basic interpersonal interactions). All had 100% positive coefficients after the three rounds, with an authority coefficient of 0.81 and coefficients of variation between 0.054 and 0.412.Conclusion:The assessment tool constructed in this study provides a new direction for quality control in clinical practice and medical insurance assessments.

Hepatocellular carcinoma is one of the common causes of tumor-related death, and it has high morbidity and mortality rates in China. Recent studies have shown that platelets are closely associated with the development of hepatocellular carcinoma. Literature review shows that platelets not only participate in hemostasis, but also act on liver cells and tumor microenvironment, promote the formation of new blood vessels, and participate in the development and progression of hepatocellular carcinoma as a cell mediator through immune response and other pathways. In addition, platelets and their derivatives can be used as potential therapeutic targets for hepatocellular carcinoma. Therefore, antiplatelet therapy is expected to become a new adjuvant strategy for the treatment of hepatocellular carcinoma, which has important clinical significance.

OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.
Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; High-Temperature Requirement A Serine Peptidase 1/genetics* ; Humans ; Macular Degeneration/genetics* ; Polymorphism, Single Nucleotide

【Objective】 To investigate the imaging features of weak response after anti-vascular endothelial growth factor (VEGF) treatment for refractory diabetic macular edema (DME) with vesicles. 【Methods】 We made a retrospective analysis of the clinical data of 120 patients with DME (120 eyes) who received anti-VEGF therapy in Ophthalmology Department of The Second Affiliated Hospital of Xi’an Jiaotong University from March 2018 to September 2019 and the same anti-VEGF medicine with the therapeutic regimen of 3+PRN. Of the 50 patients with cystoid macular edema (CME), 40 of them had a significant response and 10 had a weak response. The characteristics of optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) for the patients with weak response after anti-VEGF therapy were comparatively analyzed. 【Results】 Eyes with vesicular DME that responded weakly to anti-VEGF treatment had similar imaging characteristics. The OCT images showed impurity-independent vesicles located in the inner layer of the retina. Compared with the obvious response group, the reflection signal of the vesicle area was significantly enhanced. In early images of FFA, micro-angiomas related to vesicle formation were seen in both groups. However, in the late FFA image, the leakage intensity of vesicles in the weak response group was significantly lower than that in the obvious response group. 【Conclusion】 Vesicular DME with poor anti-VEGF treatment has the characteristics of high reflection in OCT and weak fluorescence leakage in FFA. This study is helpful for preoperative evaluation of anti-VEGF treatment.

Objective:To explore the difference of emotion recognition ability between impulsive violent criminals and the controls.Methods:Fifty-nine impulsive violent criminals were selected from 90 violent criminals in a prison.The control group consisted of 35 service workers and security guards recruited from a university.The 2 group (impulsive violent criminals group, control group) ×4 emotion (happiness, anger, sadness, fear) hybrid design was used in this study.The emotion recognition score, errors number and changed response number for each of the four emotions, including happiness, anger, sadness and fear, were obtained through an emotional expression multimorph task to investigate the difference of emotion recognition ability between the two groups.Results:Four participants with error rate more than 30％ were excluded.The effective data involved 58 impulsive violent criminals and 32 control subjects.The impulsive violent criminals had significant higher recognition scores of happiness [ (18.6±3.4) vs. (16.4±4.0), P＜0.01] and anger [ (16.2±2.4) vs. (14.1±3.2), P＜0.01] than the control group.In impulsive violent criminals, the recognition scores of facial expressions ranked from high to low were that of happiness, anger, fear and sadness (Ps＜0.05).In the control group, the recognition scores of facial expressions ranked from high to low were that of happiness, anger, fear/sadness (Ps＜0.05), but there was no significant difference between recognition scores of fear and sadness (P＞0.05).Conclusion:It suggests that the impulsive violent criminals might have a higher sensitivity to happy and angry facial expressions.

Objective To explore the functional connectivity (FC) of the fronto-striatal circuitry in patients with bulimia nervosa (BN) based on the resting-state fMRI and its correlation with the inhibitory function.Methods 27 medication-naive female patients with BN and 27 age-and education-matched female healthy control subjects were included in the study.All the subjects performed a stop signal task (SST) and underwent the resting-state fMRI scan,separately.The FC between striatal subregions and the frontal cortex was analyzed.Results Compared with healthy controls,FC between the right ventral rostral putamen (VRP) and the right supplementary motor areas (SMA) decreased (MNI coordinate:x =3,y =-15,z =51,K =27) in patients with BN.And the FC was also decreased between the right VRP and premotor area(PM) (MNI coordinate:x =27,y =0,z =57,K =44).FC between bilateral dorsal caudal putamen (DCP) (MNI coordinate:x=21,y=-6,z=48,K=43) and the right PM(MNI coordinate:x=21,y=-12,z=57,K=24) was decreased in patients with BN (P＜0.05,Alphasim corrected,voxel P＜0.005,clusters ≥ 20 voxels).FC between the right VRP and right SMA was negatively correlated with the stop signal reaction time (SSRT) in patients with BN (r=-0.595,P=0.004).The FC between right DCP and right PM was positively correlated with the impulsivity regulation subscale scores of the Eating Disorder Inventory-Ⅱ in patients with BN(r=0.483,P=0.023).Conclusion There is disrupted FC between the striatum and motor cortex in medication-naive female patients with BN based on resting-state fMRI,which may be related to impaired inhibitory control in patients with BN.