This study was performed to explore the downstream mechanism of TRIB3 mediated macrophage pro-inflammatory M1 polarization under high glucose condition.RAW264.7 were divided into CON-DMSO group,CON-SC79 group,HG-DMSO group,and HG-SC79 group.Western blot was used to detect the protein expressions of TRIB3,AKT and p-AKT.Then,RAW264.7 were divided into control vector-DMSO group,TRIB3 overexpress-DMSO group,control vector-SC79 group,TRIB3 overexpress-SC79 group,control vector-MK2206 group,and TRIB3 overexpress-MK2206 group.CCK-8 was used to detect cells activity;phase contrast microscope was used to observe cell morphology;Western blot was used to detedcted the protein expressions of TRIB3,AKT,p-AKT,iNOS and Arg-1.ELISA was used to detedcted the protein secretion of IL-1β and IL-10.Data showed that TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in HG group as compared with the CON group.Compared with corresponding control vector group,TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in TRIB3 overexpress group.Compared with corresponding DMSO group,p-AKT/AKT was significantly increased in SC79 group,and was significantly decreased in MK2206 group.Compared with TRIB3 overexpress-DMSO group,TRIB3 overexpress-SC79 group showed significant reduction in spindle shaped and irregular shaped cells,significantly decreased iNSO and IL-1β,and significantly increased IL-10.TRIB3 overexpress-MK2206 group showed further increase in spindle and irregular shaped cells,significantly decreased Arg-1 and IL-10,and significantly increased IL-β.In conclusion,TRIB3 activated under high glucose condition exerts pro-inflammatory effect by targeting AKT phosphorylation to induce M1 polarization and inhibit M2 polarization in macrophages.

Objective To establish drug use evaluation(DUE)criteria for aminocaproic acid injection,and to evaluate and analyse clinical use of aminocaproic acid injection.Methods Based on the aminocaproic acid injection drug label,DUE of aminocaproic acid injection from three aspects(indications,medications and medication results)were established with reference to relevant literature.A retrospective survey was conducted to evaluate the rationality of medication for inpatients who used aminocaproic acid injection from July 1,2021 to June 30,2022 in Fuding Hospital of Fujian University of Traditional Chinese Medicine.Results A total of 143 midical records were included.73 cases fully met the DUE criteria,70 cases did not fully meet the DUE criteria,and the unreasonable rate was 48.95%.The most common types of irrational using of aminocaproic acid injection were inappropriate timing of perioperative prevention of medication(26.57%),overcourse in perioperative prevention of medication(23.08%),and contraindications(7.69%).Conclusions The aminocaproic acid injection DUE standard established is scientific,practical,the irrational rate of aminocaproic acid injection use is relatively high in this hospital,and the management of rational use of aminocaproic acid injection needs to be strengthened.

Background: and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. Conclusions This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO₂) were compared before and after operation. In addition, the SpO₂ and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO₂ was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.
Child ; Male ; Infant, Newborn ; Humans ; Female ; Pulmonary Valve/surgery* ; Retrospective Studies ; Pulmonary Atresia/surgery* ; Heart Defects, Congenital

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

OBJECTIVE: To evaluate the diagnostic performances of salivary gland ultrasonography(SGUS)in Sjögren's syndrome(SS). METHODS: A total of 246 patients with dry mouth and/or eyes who were treated in the outpatient department and inpatient department of Rheumatology and Immunology Department of the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to January 2022 were collected. All patients received SGUS examination and scored by 2019 outcome measures in rheumatology clinical trial (OMERACT)ultrasonic scoring system.Their general information, unstimulated saliva flow rate(USFR), Schirmer test and serological test results were recorded. In the study, 193 cases had lip gland biopsy. The 2016 American College of Rheumatology(ACR)/ European League Against Rheumatism(EULAR)classification criteria were adopted as the diagnostic standard of SS. χ² test was used to compare the difference of salivary gland ultrasonic scores between the two groups. The receiver operating characteristic(ROC) curve was used to evaluate the accuracy of SGUS in diagnosing SS, and the disease characteristics of SGUS positive group and negative group in the SS patients were compared. RESULTS: A total of 175 patients were SS group according to the ACR/EULAR classification, and the remaining 71 patients were non-SS group.There was no significant difference in age [(54.2±11.8) years vs. (53.4±14.9) years, P=0.705] and female (94.4% vs.93.1%, P=1.000) between SS and non-pSS groups. A total of 109 patients were SGUS positive (≥ 2 points), of whom 104 patients met the SS diagnosis and 5 patients did not meet the SS diagnosis. The positive rate of SGUS in SS group was significantly higher than that in non-SS group (59.4% vs. 7.0%, P < 0.001). The accuracy of 2019 OMERACT ultrasonic scoring system to predict ACR/EULAR classification was good, with an area under the curve of 0.762 (95%CI 0.701-0.823). The absolute agreement between the SGUS outcome and ACR-EULAR classification was 69.1%(170/246), with a sensiti-vity of 59.4%(104/175), specificity of 93%(66/71), positive predictive value of 95.4%(104/109) and negative predictive value of 48.2% (66/137). A total of 81 patients were positive SGUS combined with anti-SSA antibody, 100% (81/81) fulfilled the ACR-EULAR criteria, 85 patients were negative SGUS and anti SSA antibody, and 60 patients(70.6%, 60/85) did not fulfil the ACR-EULAR criteria. SGUS positive group had higher antinuclear antibody(ANA) positive rate(83.1% vs. 98.1%, P < 0.001) in the patients with SS. CONCLUSION The OMERACT ultrasonic scoring system has high diagnostic value in SS. The combination of SGUS and anti-SSA antibody can improve the diagnostic value.
Humans ; Female ; Adult ; Middle Aged ; Aged ; Sjogren's Syndrome/diagnostic imaging* ; Sensitivity and Specificity ; China ; Salivary Glands/pathology* ; Ultrasonography/methods*

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Gene Expression ; Genes, ras ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Oncogene Fusion ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Retrospective Studies ; Young Adult

OBJECTIVE: To investigate the effectiveness and safety of low concentration dithiothreitol (DTT) in removing the interference of monoclonal anti-CD38 on transfusion compatibility testing, and develop a reasonable clinical transfusion strategy. METHODS: The blood type, direct antiglobulin testing (DAT) and antibody screening were tested according to standard methods. Antibody screening cells and donor's red blood cells were treated by DTT 0.2, 0.1, 0.05, 0.02, 0.01 and 0.005 mol/L, and antibody screening and cross-matching of serums after monoclonal anti-CD38 treatment were performed by anti-human globulin card. RESULTS: The 0.01 mol/L DTT at 37℃ for 30 minutes could remove the effect of monoclonal anti-CD38 on antibody screening and cross-matching, meanwhile retain their effectiveness in detecting anti-K, anti-LW, anti-JMH, anti-Lu^b, anti-e, anti-Di^a and anti-Jk^a alloantibodies. All the 10 patients had no acute or delayed haemolytic transfusion reactions and their routine blood tests showed that the red blood cells transfusion was effective. CONCLUSION The 0.01 mol/L DTT is a safe and effective method for removing the interference of monoclonal anti-CD38 with transfusion compatibility testing, while retaining the ability to detect most alloantibodies.
Antibodies, Monoclonal/pharmacology* ; Blood Grouping and Crossmatching ; Blood Transfusion ; Dithiothreitol/pharmacology* ; Erythrocytes ; Humans ; Isoantibodies/pharmacology*

OBJECTIVE: To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay. RESULTS: Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones. CONCLUSION The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.
Child ; Child, Preschool ; Female ; Gastrointestinal Tract ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Male ; Plasma