الملخص
Objective:To detect the concentration of various cytokines in aqueous humor of patients with diabetes retinopathy (DR) with Luminex liquid chip, and analyze the relationship between the cytokines and the occurrence and development of DR.Methods:A cross-sectional study was conducted.Sixty-three DR patients (97 eyes) treated with anti-vascular endothelial growth factor (VEGF) drugs in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from March 1, 2019 to December 31, 2019 were enrolled as DR group, including 38 nonproliferative DR (NPDR) eyes in NPDR group and 59 proliferative DR (PDR) eyes in PDR group, 39 eyes in photocoagulation group and 58 eyes in non-photocoagulation group.Twenty-seven patients (31 eyes) hospitalized for cataract surgery at the same time were collected as the control group.Aqueous humor was extracted during the operation, and Luminex liquid chip was used to detect the concentrations of vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, angiopoietin-like protein 4 (ANGPTL4), interleukin-6 (IL-6), IL-8, IL-1β, monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in aqueous humor.The concentrations of various cytokines of different groups were compared, and the correlation among various aqueous humor cytokines was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of First Affiliated Hospital of Guangzhou University of Chinese Medicine (No.Y[2019]230). Written informed consent was obtained from each patient.Results:The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in DR group were significantly higher and the concentration of IL-1β was significantly lower than those of control group ( Z=-4.747, -5.164, -3.373, -8.062, -4.535, -5.954, -5.098, -3.228, -5.954, all at P<0.01). The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8 and MCP-1 of the photocoagulation and non-photocoagulation groups were higher and the concentration of IL-1β was significantly lower than those in the control group (all at P<0.017). The concentration of ICAM-1 in the photocoagulation group was significantly higher than that in the control group ( P<0.017). The concentrations of PLGF, PDGF-AA and ANGPTL4 of PDR group were higher than those of NPDR group, and the differences were statistically significant ( Z=-2.291, -3.396, -2.276, all at P<0.05). VEGF-A was positively correlated with the other cytokines except ICAM-1 ( rs=0.237-0.540, all at P<0.05). ANGPTL4 was positively correlated with the other cytokines except IL-1β ( rs=0.361-0.733, all at P<0.01). Conclusions:The occurrence and development of DR are closely related to VEGF family, PDGF family, ANGPTL family and inflammatory factors.The concentrations of PLGF, PDGF-AA and ANGPTL4 are higher in PDR eyes.There are close and complex relationships among a variety of cytokines in the eyes of DR patients.
الملخص
Background/Aims@#Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). @*Methods@#Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. @*Results@#A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. @*Conclusions@#Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.
الملخص
Objective:To compare the consistency between bioelectrical impedance analysis(BIA)and dual-energy X-ray absorptiometry(DXA)in skeletal muscle mass assessment in elderly patients with advanced chronic kidney disease(CKD), and to provide a basis for accurate clinical diagnosis of sarcopenia.Methods:Elderly patients with advanced CKD at the Department of Nephrology of Shanghai Sixth People's Hospital were included.Parameters for physical performance included handgrip strength and gait speed, and body muscle mass was measured by DXA and multifrequency BIA.The consistency between the two methods was assessed by the intraclass correlation coefficient, Bland-Altman analysis and kappa coefficient test.Results:This study included 67 elderly patients with advanced CKD with a mean age of(70.7±6.1)years and an average BMI of(24.6±3.5)kg/m 2.The proportion of enrolled male patients was 61.2% and the mean estimated glomerular filtration rate was(27.7±12.7)ml·min -1·1.73m -2.The intraclass correlation coefficients of muscle mass and appendicular skeletal-muscle mass index(ASMI)measured by BIA and DXA ranged from 0.81 to 0.90.Bland-Altman analysis showed that BIA overestimated muscle mass against DXA, and the mean difference in ASMI was(0.44±0.13)kg/m 2.In addition, there was a moderate agreement between the two measurement methods for determining muscle loss(Kappa=0.47). Conclusions:BIA and DXA offer a fair level of consistency in the assessment of muscle mass in elderly patients with advanced CKD.However, compared with DXA, BIA overestimates muscle mass in elderly patients with CKD.
الملخص
Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.
الملخص
Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.
الملخص
Bacitracin is a broad-spectrum antibiotics mainly produced by Bacillus, and is used as veterinary medicine in the fields of livestock and poultry breeding. Insufficient supply of precursor amino acids might be an important factor that hinders high-level microbial production of bacitracin. We investigated the effect of strengthening L-cysteine supply on bacitracin production by an industrial bacitracin producer, Bacillus licheniformis DW2. Overexpression of cysK encoding L-cysteine synthase led to a 9.17% increase of the bacitracin titer. Moreover, overexpression of cysE encoding L-serine acetyltransferase and cysP encoding thiosulfate/sulfate intracellular transporter increased the bacitracin titers by 7.23% and 8.52%, respectively. Moreover, overexpression of a putative cystine importer TcyP led to a 29.19% increase of intracellular L-cysteine, and bacitracin titer was increased by 7.79%. Subsequently, the strong promoter PbacA was used to replace the promoters of genes cysP, cysE and tcyP in strain DW2::ysK, respectively. The resulted strain CYS4 (DW2::cysK-PbacA-(cysP)-PbacA(cysE)- PbacA(tcyP) produced 910.02 U/mL bacitracin, which was 21.10% higher than that of the original strain DW2 (747.71 U/mL). Together with the experiments in 3 L fermenters, this research demonstrated that enhancing intracellular L-cysteine supply is an effective strategy to increase bacitracin production of B. licheniformis.
الموضوعات
Amino Acids , Bacillus licheniformis/genetics , Bacitracin , Cysteine , Metabolic Engineeringالملخص
Objective:To investigate the effect of artificial dermis combined with KCI negative pressure suction device in the repair of scalp defect with skull exposure after the operation of scalp malignancy.Methods:From January 2016 to June 2018, 18 patients with scalp defect and skull exposure after scalp malignant tumor surgery were treated with artificial dermis combined with KCI negative pressure suction device.Results:Eighten patients had good wound healing after the first stage of surgery, and no infection occurred. The time for artificial dermis to complete granulation was 10-14 days, with an average of 12.1 days. After the second stage of skin grafting, the skin graft had a survival rate of 100%, with uniform color and good elasticity, without obvious scar hyperplasia or contracture. The postoperative follow-up period was 6 to 2 months, all the patients healed well without tumor recurrence, with good skin elasticity and friction-resistant, and they were satisfied.Conclusions:Artificial dermis combined with KCI negative pressure suction device is an effective and simple method to repair the scalp defect with skull exposure after tumor surgery.
الملخص
Objective:To investigate the clinical characteristics and related risk factors of sarcopenia in elderly patients undergoing maintenance hemodialysis.Methods:This was a retrospectively study involving 135 elderly hemodialysis patients aged(70.6±7.7)years, with 46(34.1%)females and a mean hemodialysis duration of(3.2±2.9)years, at Shanghai Sixth People's Hospital.The incidence of sarcopenia in patients was examined by measuring handgrip strength, walking speed and muscle mass of the limbs using bioelectrical impedance analysis.Related risk factors were analyzed with univariate and multivariate logistic regression analysis.Results:Among 135 elderly hemodialysis patients, the incidence of sarcopenia was 62.9%(85 cases), and severe sarcopenia cases accounted for 44.4%(60 cases). Compared with the non-sarcopenia group, patients with sarcopenia were older, had lower body mass index(BMI)and handgrip strength, walked more slowly and had less muscle mass in their limbs.Advanced age, low BMI and long dialysis duration were correlated with the high incidence of sarcopenia in elderly dialysis patients.The odds ratio( OR)for sarcopenia increased by 12% per year, and the OR decreased by 32% with an increase of 1.0 kg/m 2 in BMI.Advanced age and lower BMI were also correlated with a high incidence of severe sarcopenia( OR=1.12, 95% CI: 1.05~1.18; OR=0.84, 95% CI: 0.74~0.95; all P<0.01). Conclusions:The incidence of sarcopenia is high in elderly hemodialysis patients and is closely related to advanced age and low body weight.Improving nutritional status and avoiding low body weight will help reduce the occurrence and development of sarcopenia in elderly hemodialysis patients.
الملخص
Objective:To explore the clinical manifestation, efficacy and treatment strategies in patients with severe warm autoimmune hemolytic anemia (w-AIHA).Methods:A total of 21 patients with w-AIHA who were hospitalized in Children′s Hospital of Capital Institute of Pediatrics from June 2007 to March 2019 were included, and the clinical characteristics, treatment strategies and responses were retrospectively analyzed.Results:A total of 21 children with severe w-AIHA had an average age of 8.0 (2.5, 20.0) months and a follow-up time of 33.0 (18.5, 110.0) months.In 10 (47.6%) cases, the hemoglobin levels were lower than 30 g/L.Evans′ syndrome was diagnosed in five(23.8%) cases.Five (23.8%) cases were secondary cases.Nine (42.8%) cases had a previous infection history and two cases were pollen-induced.Five (23.8%) cases had hemolytic crisis.A total of 12 (57.1%) cases had cross-matching difficulty.Eight (38.1%) cases were admitted to the ICU, and five (23.8%) cases had shock.All children received corticosteroids and intravenous immunoglobulin, 16 (76.2%) cases were treated with second-line regimens (cyclophosphamide and rituximab, etc.), 15 cases had complete response, three cases had partial response and three cases had no response and died.Conclusion:Infection is an important predisposing factor in children with severe w-AIHA, and secondary cases have a higher proportion, mainly caused by immunodeficiency disease.Patients tend to have a high incidence of hemolytic crisis and have difficulty in matching and transfusion.Therefore, transfusion is the key for successful rescue.It is suggested that children with severe w-AIHA require ICU admission for early monitoring and rituximab should be applied in advance to ensure successful transfusion.
الملخص
Objective:To investigate the surgical indications of gallbladder polyps.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 272 patients with gallbladder polyps who underwent cholecystectomy in 11 medical centers from January 2015 to December 2019 were collected, including 585 in the First Affiliated Hospital of Xi′an Jiaotong University, 352 in No. 215 Hospital of Shaanxi Nuclear Industry, 332 in the First People′s Hospital of Xianyang, 233 in Shaanxi Provincial People′s Hospital, 152 in the Second Affiliated Hospital of Xi′an Jiaotong University, 138 in Xianyang Hospital of Yan′an University, 137 in People′s Hospital of Baoji, 125 in Hanzhong Central Hospital, 95 in Baoji Central Hospital, 72 in Ankang Central Hospital, 51 in Yulin No.2 Hospital. There were 887 males and 1 385 females, aged (48±12)years, with a range from 12 to 86 years. Observation indicators: (1) surgical treatment, pathological examination and hospitalization; (2) follow-up and complications; (3) comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps; (4) comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis; (5) analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis; (6) construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Follow-up using outpatient examination or telephone interview was conducted to detect complications and survival of patients up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the rank-sum test. Ordinal data was analyzed using the rank-sum test of multi-samples. Analysis of influence factors for the incidence of neoplastic polyps was conducted after excluding missing data of CEA and CA19-9. Univariate analysis was conducted using the chi-square test or rank-sum test of multi-samples, and multivariate analysis was conducted using Logistic regression model. Based on Logistic regression model multivariate analysis, the nomogram prediction model was constructed using the R 3.6.0 version software. Results:(1) Surgical treatment, pathological examination and hospitalization: of the 2 272 patients, 2 199 cases underwent laparoscopic cholecystectomy, 43 cases underwent open cholecystectomy, 28 cases underwent radical resection for gallbladder carcinoma, and 2 cases underwent laparoscopic gallbladder preservation and polypectomy. There were 1 050 of the 2 272 patients undergoing intraoperative frozen section examination. Results of pathological examination showed that 1 953 of the 2 272 patients had non-neoplastic polyps including 1 681 cases with cholesterol polyps and 272 cases with inflammatory polyps; 319 cases had neoplastic polyps including 274 with benign polyps (93 cases with adenoma, 66 cases with adenomyoma, 81 cases with adenoma-like hyperplasia, 34 cases with adenoma combined with intraepithelial neoplasia); and 45 cases had malignant polyps including 43 cases with adenocarcinoma, 1 case with adenosquamous carcinoma and 1 case with sarcomatoid carcinoma. The duration of postoperative hospital stay of 2 272 patients was 3 days(range, 1 to 27 days). (2) Follow-up and complications: of the 2 272 patients, 1 932 were followed up for 3.5 to 63.5 months, with a median follow-up time of 31.0 months. During the follow-up, 180 patients had short-term complications and 170 patients had long-term complications. (3) Comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps: cases with age ≤50 years or >50 years, cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, CA125, cases with single or multiple polyps in preoperative ultrasonography examination, cases with diameter of polyps in preoperative ultrasonography examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasono-graphy examination as nodular, papillary, globular or mulberry-like, cases undergoing or not undergoing intraoperative frozen section examination, cases with diameter of polyps in postoperative pathological examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with gallbladder wall thickness in postoperative pathological examination as ≤4 mm or >4 mm of the 1 953 patients with non-neoplastic polyps were 1 118, 835, 1 027, 422, 230, 274, 2.0 mg/L(range, 0.2-8.6 mg/L), 14.5 U/mL(range, 2.6-116.4 U/mL), 10.5 U/mL(range, 1.2-58.7 U/mL), 658, 1 295, 674, 741, 413, 125, 1 389, 564, 407, 1 119, 292, 135, 832, 1 121, 698, 774, 385, 96, 1 719, 234, respectively. The above indicators of the 319 patients with neoplastic polyps were 160, 159, 204, 55, 26, 34, 2.9 mg/L(range, 0.2-28.8 mg/L), 19.7 U/mL(range, 3.5-437.1 U/mL), 15.0 U/mL(range, 1.0-945.0 U/mL), 203, 116, 49, 59, 100, 111, 154, 165, 92, 153, 49, 25, 218, 101, 53, 85, 90, 91, 263, 56, respectively. There were significant differences in the above indicators between the non-neoplastic polyps and neoplastic polyps patients ( χ2=5.599, Z=-3.668, -2.407, -3.023, -3.403, χ2=104.474, Z=-13.367, χ2=65.676, 12.622, 73.075, Z=-11.874, χ2=7.649, P<0.05). (4) Comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis: after excluding 311 of the 2 272 patients with cholecystolithiasis, there were 706 cases with gallbladder polyp diameter of 7 to 9 mm, 459 cases with gallbladder polyp diameter of 10 to 12 mm, and 205 cases with gallbladder polyp diameter ≥13 mm, respectively. Cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, cases with single or multiple polyps in preoperative ultrasonography examination, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasonography examination as nodular, papillary, globular or mulberry-like, cases with echo intensity of preoperative ultrasonography examination as slightly strong, medium or weak, cases undergoing or not undergoing intraoperative frozen section examination, and cases with pathological types of polyps as non-neoplastic polyps, benign polyps or malignant polyps of the 706 patients with gallbladder polyp diameter of 7 to 9 mm were 291, 170, 107, 138, 2.2 mg/L(range, 0.5-8.6 mg/L), 21.0 U/mL(range, 2.8-116.4 U/mL), 207, 499, 620, 86, 118, 463, 75, 50, 252, 410, 44, 379, 327, 657, 49, 0, respectively. The above indicators of the 459 patients with gallbladder polyp diameter of 10 to 12 mm were 267, 85, 43, 64, 1.6 mg/L(range, 0.4-9.3 mg/L), 10.4 U/mL(range, 3.3-354.0 U/mL), 205, 254, 237, 222, 158, 223, 51, 27, 222, 213, 24, 263, 196, 373, 79, 7, respectively. The above indicators of the 205 patients with gallbladder polyp diameter ≥13 mm were 128, 38, 20, 19, 2.1 mg/L(range, 0.6-28.8 mg/L), 10.2 U/mL(range, 3.6-307.0 U/mL), 120, 85, 75, 130, 68, 97, 22, 18, 98, 95, 12, 148, 57, 113, 71, 21, respectively. There were significant differences in the above indicators among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥ 13 mm ( χ2=46.482, 8.093, 39.504, 66.971, 277.043, 60.945, 19.672, 22.340, 197.854, P<0.05). (5) Analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: of the 459 patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis, there were 373 cases with non-neoplastic polyps, and 86 cases with neoplastic polyps, respectively. Results of univariate analysis showed that CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( χ2=10.342, 5.616, 20.009, Z=-4.352, χ2=6.203, P<0.05). Results of multivariate analysis showed that CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( odds ratio=8.423, 0.082, 0.337, 3.694, 2.318, 95% confidence interval: 1.547-45.843, 0.015-0.443, 0.198-0.575, 1.987-6.866, 1.372-3.916, P<0.05). (6) Construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were imported into R 3.6.0 version software to establish the nomogram prediction model for neoplastic polyps. The results showed the score for CEA>5.0 mg/L, CA19-9>39.0 U/mL, cases with single polyp in preoperative ultrasonography examination, cases with polyp diameter of 10 mm in preoperative ultrasonography examination, cases with polyp diameter of 11 mm in preoperative ultrasonography examination, cases with polyp diameter of 12 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were 25, 27, 100, 0, 26, 72, 98 in the nomogram prediction model, respectively. The C-index of nomogram prediction model was 0.768. Result of nomogram prediction model showed that the incidence of tumor polyps was 0, 6% and 10% in patients with multiple and pedicled gallbladder polyps with diameter of 10, 11, 12 mm and with CEA ≤5.0 mg/L and CA19-9 ≤39.0 U/mL, the incidence of tumor polyps was 43%, 53% and 70% in patients with single and broad base gallbladder polyps with diameter of 10, 11, 12 mm. The calibration curve showed that the probability of the nomogram prediction model predicting neoplastic polyps was nearly consistent with the actual probability. Conclusions:CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination are independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Cholecystectomy should be performed in time for patients with single and broad based gallbladder polyps with diameter of 10, 11, 12 mm.
الملخص
Bacitracin is a broad-spectrum cyclic peptide antibiotic, and mainly produced by Bacillus. Energy metabolism plays as a critical role in high-level production of target metabolites. In this study, Bacillus licheniformis DW2, an industrial strain for bacitracin production, was served as the original strain. First, our results confirmed that elimination of cytochrome bd oxidase branch via deleting gene cydB benefited bacitracin synthesis. Bacitracin titer and ATP content were increased by 10.97% and 22.96%, compared with those of original strain, respectively. Then, strengthening cytochrome aa3 oxidase branch via overexpressing gene qoxA was conducive to bacitracin production. Bacitracin titer and ATP content were increased by 18.97% and 34.00%, respectively. In addition, strengthening ADP synthesis supply is also proven as an effective strategy to promote intracellular ATP accumulation, overexpression of adenosine kinase DcK and adenylate kinase AdK could all improve bacitracin titers, among which, dck overexpression strain showed the better performance, and bacitracin titer was increased by 16.78%. Based on the above individual methods, a method of combining the deletion of gene cydB and overexpression of genes qoxA, dck were used to enhance ATP content of cells to 39.54 nmol/L, increased by 49.32% compared to original strain, and bacitracin titer produced by the final strain DW2-CQD (DW2ΔcydB::qoxA::dck) was 954.25 U/mL, increased by 21.66%. The bacitracin titer produced per cell was 2.11 U/CFU, increased by 11.05%. Collectively, this study demonstrates that improving ATP content was an efficient strategy to improve bacitracin production, and a promising strain B. licheniformis DW2-CQD was attained for industrial production of bacitracin.
الموضوعات
Bacillus licheniformis , Metabolism , Bacitracin , Energy Metabolism , Genetics , Industrial Microbiology , Methodsالملخص
Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mice. These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
الموضوعات
Animals , Mice , Bone Resorption , Genetics , Mice, Inbred C57BL , Osteoclasts , Osteogenesis , RANK Ligand , RNA, Long Noncoding , Geneticsالملخص
Objective To investigate the effects of adoptive reinfusion of regulatory T cell (Treg) on the recovery of islet function and graft survival time after islet allograft transplantation. Methods The diabetic model was established using C57BL/6 mice as recipients, and Balb/c mice were chosen as donors for islet allografts transplantation beneath the renal capsule. The recipient mice were divided into 3 groups and 3 mice in each group according to different processing Methods: Treg experiment group (Treg group, 1×106 Treg cells were injected via tail vein at 1 d before operation), positive control group [sirolimus (SRL) group, SRL at a dose of 300 μg/(kg·d) was intragastrically given every day from 1 d before operation] and blank control group (control group, an equivalent volume of normal saline was intragastrically given every day from 1 d before operation). Enzyme-linked immune absorbent assay (ELISA) was used to detect the changes of blood glucose and C-peptide in mice within 14 days after transplantation. In vivo imaging technique was used to dynamically monitor the survival of mice within 14 days after transplantation. Results In each group, the blood glucose levels at postoperative 3 d were significantly decreased compared with those before transplantation (all P < 0.001). At postoperative 1 d, the C-peptide levels showed an explosive rise to varying degree in each group. At postoperative 3 d, the C-peptide levels in each group were significantly higher than that before operation (all P < 0.001). At the end of the observation period at 14 d after operation, the C-peptide levels in the SRL and Treg groups were (427±50) pmol/L and (833±57) pmol/L, relatively higher than that in the control group. But the blood glucose levels were (14.5±0.5) mmol/L and (12.1±0.6) mmol/L, significantly lower than that in the control group (all P < 0.001). Compared with the SRL group, the explosive release amount of C-peptide was significantly lower, the declining trend was more remarkably stable, and the C-peptide level was considerably higher in the Treg group at the end of the observation period (all P < 0.001). At postoperative 14 d, the grafts were almost completely apoptotic in the control group, over 50% of the grafts survived in the SRL group, and over 80% of the grafts survived in the Treg group. Conclusions Adoptive reinfusion of Treg cells can effectively protect islet grafts, prolong the survival time of grafts, and maintain the normal levels of blood glucose and C-peptide in the recipient mice.
الملخص
Objective@#To explore the diagnosis value of late gadolinium enhancement(LGE) detected by magnetic resonance imaging(MRI) in acute myocardial infarction(AMI) patients.@*Methods@#The clinical and MRI data of 52 AMI patients hospitalized from January 2016 to July 2017 in our hospital were retrospectively analyzed. All patients received medication and revascularization therapies after admission and cardiac magnetic resonance examination was performed within 1 week after admission. According to whether there was LGE, AMI patients were divided into LGE(+) group(33 cases) and LGE(-) group(19 cases). According to the existence of microvascular obstruction(MVO) and/or intramyocardial hemorrhage(IMH),LGE(+) patients were divided into MVO/IMH(+) group(18 cases) and MVO/IMH(-) group(15 cases).@*Results@#(1)There were no statistical significance between the LGE(+)group and LGE(-)group in the age, gender,smoking history, hypertension, diabetes mellitus, dyslipidemia, ventricular arrhythmia, culprit vessel, left ventricular end-diastolic volume(LVEDV), and left ventricular end-systolic volume(LVESV) (all P>0.05). The left ventricular ejection fraction was significantly lower in LGE(+) group than in LGE(-) group( (38.7±17.6) % vs. (51.2±7.9)%, P=0.001). (2)The infarct size was positively correlated with LVEDV and LVESV(r=0.436,P=0.011;r=0.479,P=0.005,respectively), and negatively correlated with left ventricular ejection fraction (r=-0.641, P<0.001) in LGE(+) group. (3) The infarct size, LVEDV, and LVESV were significantly higher in MVO/IMH(+) group thanin MVO/IMH(-) group ((26.5±7.3)%vs. (16.2±8.3)%, P=0.001; (145.7±40.9)ml vs. (112.2±23.8)ml,P=0.009; (90.0±30.8)ml vs. (61.4±19.0)ml,P=0.004, respectively), and the left ventricular ejection fraction was significantly lower in MVO/IMH(+) group than in MVO/IMH(-) group ((29.8±15.0)% vs. (49.3±14.5)%, P=0.001).@*Conclusions@#LGE detected bycardiac magnetic resonance can provide useful information on the myocardial necrosis extent of AMI patients. Presence of MVO/IMH in LGE(+) patients is linked with larger infarct size and worse cardiac dysfunction in AMI patients.
الملخص
Bacitracin is a broad-spectrum polypeptide antibiotic, which is formed by 11 amino acids residues. Precursor amino acids supply might be the limit factor during bacitracin fermentation. First, our results demonstrated that increasing Ile and Leu supplies were regarded as the efficient strategies for the enhanced titer of bacitracin. Then, the amino acid permease YhdG, which was identified as the BCAA permease, was deleted and overexpressed in DW2, respectively. Our results showed that knocking out of permease YhdG could improve bacitracin production remarkablely. The bacitracin titer of the yhdG deficient strain DW2ΔyhdG reached 917.35 U/mL by flask fermentation, increased by 11% compared with that of DW2. In addition, the bacitracin titer was decreased by 25% in the YhdG overexpressed strain. Meanwhile, the intracellular concentrations of BCAA were higher than DW2 during the biosynthesis of bacitracin. The above results suggested that the permease YhdG might act as an exporter for branched chain amino acids in B. licheniformis DW2. Taken together, the increasing intracellular concentrations of branched chain amino acids by deleting amino acid permease YhdG could improve bacitracin titer. This study provided a new strategy for high-level production of bacitracin.
الملخص
Objective To evaluate the accuracy of the biometry using immersion B scan and partial coherence interferometry (Lenstar LS900) for the axial length (AL) of silicone oil-filled eyes respectively.Methods Thirty-five silicone oil-filled eyes (38 patients) were included in the study.All of these eyes underwent silicone oil removal,cataract extraction and intraocular lenses implantation.The AL of all the silicone oil-filled eyes was measured with A/B-scan ultrasound and Lenstar LS900 before operation and with Lenstar LS900 after operation.The measured distance was compared respectively.The method of immersion B-scan guided with respective sonic velocity.AL was the sum of corneal thickness,anterior chamber depth,lens thickness,the apparent length of oil bubble (velocity values 996 m/s),the depth of the water layer beneath the oil bubble.Results Thirty-one eyes were measured with Lenstar LS900 before silicone oil removal,and the mean AL was (24.12± 1.70) mm,7 eyes failed to get the results before the operation;36 eyes were measured with Lenstar LS900 after silicone oil removal,and the mean AL was (24.45±1.89) mm.All eyes were measured with B-scan before silicone oil removal,and the mean AL was (24.87±2.52) mm.The difference (31 eyes) of AL measurement before silicone oil removal by two methods was (-0.00±0.09) mm;the difference (31 eyes) between pre-and post-surgical AL measurement with Lenstar LS900 was (0.02±0.07) mm;the difference (36 eyes) between pre-surgical AL measured with B-scan and post-surgical AL measured with Lenstar LS900 was (-0.02±0.11) mm.All the differences were not statistically significant (t=-0.205,1.752,-1.280;P＞ 0.05).The consistency of the results measured by two methods was well in Bland-Ahamn analysis.Conclusions Measurement results of AL between immersion B-scan guided with respective sonic velocity and Lenstar LS900 are high repeatability on silicone oil-filled eyes.The AL of silicone oil-filled eyes can be measured reliably by immersion B-scan guided with respective sonic velocity.
الملخص
Animal operation training is an important course that medical students need to study before they get into their clinical practice.Because there is no cavity mirror operation training standard and teaching experience for interns,we have put forward and conducted the animal laparoscopic teaching applications in surgery teaching,and evaluated the teaching effect.Through training,the clinical medical students have personally experienced and learnt basic operation skills of laparoscopic surgery,which is an organic link from textbooks to clinical practice,and at the same time they have improved the ability of clinical practice,cultivate and strengthen their interest in laparoscopic surgical skills training and operation,which help them lay a good foundation for clinical practice.
الملخص
Objective To analyze the microRNA-155 (miR-155) expression in hepatocellular carcinoma (HCC),and to assess its correlation with clinicopathological parameters and its prognostic significance.Methods MiR-155 expression was detected in specimens of HCC and its adjacent non-tumorous liver tissues in 124 HCC patients by real-time PCR.The expression was also detected in different HCC cell lines.The Kaplan-Meier Curve was used to analyze survival of HCC patients.Gain-and loss-of-function studies were used to determine whether miR-155 impact cell cycle,cell proliferation and apoptosis of HCC cells.Results Expression of miR-155 in HCC tissues was significantly elevated when compared with that in the adjacent non-tumor liver tissues (P ＜ 0.05).MiR-155 expression was significantly higher in different HCC cell lines (P ＜ 0.05) than that in normal liver cells.MiR-155 overexpression was significantly correlated with large tumor size (P ＜ 0.05),high histological grade (P ＜ 0.05) and advanced tumor stage (P ＜ 0.05).Patients with high miR-155 expression had significantly decreased overall survival (P ＜ 0.05) and disease-free survival (P ＜ 0.05).Upregnlation of miR-155 promoted cell cycle transition from G1 to S phase (P ＜ 0.05),increased cell proliferation (P ＜ 0.05) and apoptosis resistance (P ＜ 0.05) in Hep3B cells.Downregulation of miR-155 resulted in G1 arrest,apoptosis promotion and proliferation reduction in SMMC-7721 cells (P ＜ 0.05).Conclusion MiR-155 can be used as a prognostic marker for HCC patients,and target therapy on miR-155 can be used as a potential option to prevent HCC progression.
الملخص
Objective To investigate the protective effect of Gui Zhi Fuling Jiaonang on endurance to ischemia and hypoxia .Methods Mice were randomized into four groups :control group ,positive drug control group ,Gui Zhi Fuling Jiaonang high‐dose group (0 .93 g/kg) ,and Gui Zhi Fuling Jiaonang low‐dose group (0 .465 g/kg) . All mice were treated with corresponding drugs for 7 days .The hypoxia mice model was established through hypoxia in the closed jars , cerebral anoxia by decapitation , poisoning with sodium nitrite and isoprenaline . Then the hypoxia‐ischemia rat model was established by injecting isoproterenol . The anti‐hypoxic effects were observed . Results Compared with control group ,Gui Zhi Fuling Jiaonang high‐dose group (0 .93 g/kg) had a tendency to extend the survival time of mice model established through hypoxia in the closed jars ;Gui Zhi Fuling Jiaonang high‐dose (0 .93 g/kg) and low‐dose (0 .465 g/kg) groups had a tendency to extend the survival time of mice model established through cerebral anoxia by decapitation (P>0 .05) .Compared with that in control group ,the survival time of mice in Gui Zhi Fuling Jiaonang low‐dose group under poisoning with sodium nitrite and Gui Zhi Fuling Jiaonang high‐dose group under poisoning with isoprenaline were significantly prolonged .Besides ,Gui Zhi Fuling Jiaonang relieved myocardial tissue damage caused by ischemia and hypoxia ( P< 0 .05 ) .Conclusion Gui Zhi Fuling Jiaonang has an obviously protective effect on isoprenaline‐induced hypoxia and myocardial ischemia .
الملخص
<p><b>OBJECTIVE</b>To observe the efficacy and adverse reaction of the improvement program of cladribine combined with cytarabine (2-CdA+Ara-C) in treatment of children with refractory high-risk Langerhans cell histiocytosis (LCH).</p><p><b>METHODS</b>13 patients with refractory high-risk LCH or recurrent LCH were treated by combined 2-CdA+Ara-C chemotherapy. The treatment efficacy and the disease state in the process were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009). The drug toxicity was evaluated according to the Common Terminology Criteria Adverse Events Version 4.0 (CTCAE v4.0, 2009).</p><p><b>RESULTS</b>Of 13 patients, 10 cases achieved non active disease (NAD); 2 patients with liver cirrhosis before the improvement program with CIP-LCH-2012 gave up the treatment after 1 course of therapy; 1 patient died of infectious shock after chemotherapy with severe pulmonary infection and intestinal infection. All 13 patients had grade 3 of blood and lymphatic system toxicity; 10 patients had grade 1 of hepatobiliary and gastrointestinal side effects; 3 patients with liver cirrhosis before the improvement program had grade 2 or grade 3 of hepatobiliary system and gastrointestinal system side effects, including 1 patient of death.</p><p><b>CONCLUSION</b>The improvement program of CIP-LCH-2012 had significant efficacy for children with refractory high-risk and relapsed LCH. The cladribine-associated toxicity was of significant myelosuppression, which may be tolerated in the most children patients. The program could be considered as a recommended salvage therapy for multi-system LCH (MS-LCH) after failure of first-line therapy, and as a first-line therapy for MS-LCH with risk organ injury. The program should be used with caution or dose-adjustment consideration for pre-treatment of severe organ damage exist, especially cirrhosis.</p>