OBJECTIVE: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

Objective To clarify whether the use of dynamic coronary artery roadmap(DCR)technology in a low-dose mode with 7.5 frames per second during coronary intervention can further reduce the total radiation dose,fluoroscopy time,and contrast agent usage.Methods A total of 94 patients,who received coronary angiography at the Shanghai Tongji Hospital of China between July 2022 and December 2022,were enrolled in this study.The patients were randomly divided into DCR group(n=53)and control group(n=41).DCR technology was used in the DCR group to guide the performance of percutaneous coronary intervention(PCI),while low-dose mode coronary angiography was adopted in the control group.The total air kerma(AK),dose-area product(DAP),intraoperative fluoroscopy time,and contrast agent usage were compared between the two groups.Results In the DCR group AK was(597.9±222.8)mGy,which was significantly lower than(717.0±326.8)mGy in the control group(P=0.039);DAP was(33.2±13.3)Gycm2/s,which was also remarkably lower than(41.3±21.5)Gycm2/s in the control group(P=0.027).In the DCR group and the control group,the intraoperative fluoroscopy time was(9.8± 3.3)min and(12.1±4.3)min respectively(P＜0.01),and the contrast agent usage was(122.3±19.0)mL and(130.5± 28.5)mL respectively(P=0.116).Conclusion In a low-dose mode during coronary intervention,the use of DCR technology can further reduce radiation dose,fluoroscopy time,and contrast agent usage.(J Intervent Radiol,2024,33:236-239)

OBJECTIVE To explore the practicality of the pharmaceutical pathway for prophylactic use of antibiotics during the perioperative period of class Ⅰ neurosurgery incisions. METHODS The previously established pharmaceutical pathway for the prophylactic use of antibiotics in the perioperative period of class Ⅰ neurosurgery incisions was used to retrospectively evaluate the prophylactic use of antibiotics in 127 cases. The “antibiotics prophylactic use scoring system” in the pharmaceutical pathway was used to conduct preoperative scoring， and the patient’s actual antibiotics use was compared and analyzed in combination with existing Guiding Principles for Clinical Application of Antibiotics （2015 Edition） （hereinafter referred to as the Guiding Principles）. The pharmaceutical pathway also innovatively proposes key points for improvement in terms of the frequency of adding antibiotics during surgery and the duration of prophylactic use of antibiotics after surgery. By comparing with the actual medication situation of patients， the direction for updating the Guiding Principles was explored. RESULTS According to the retrospective analysis results， for neurosurgery class Ⅰ incision surgery， in addition to the preoperative prophylactic use of antibacterial drugs for skull mass resection and carotid endarterectomy recommended in the guidelines， endoscopic trigeminal microvascular decompression， arthroscopy and other specific joint examinations， spinal nerve Radical decompression， endoscopic lumbar nucleectomy， dural repair， and spinal canal decompression can also be further explored about the situation of not using antibacterial prophylaxis before surgery； at the same time， for the patients undergoing class Ⅰ neurosurgery incisions， the use of antibiotics during and after surgery may be considered for a second addition of antibiotics， taking into account the surgical time. If cerebrospinal fluid leakage occurred after surgery， it is recommended to extend the duration of prophylactic use of antibiotics appropriately. CONCLUSIONS The application of pharmaceutical pathways can provide more targeted analysis of key points in the prevention of antibiotic use， which promotes the transformation of perioperative antibiotics management for class Ⅰ incisions from “qualitative， empirical” management to “quantitative， scientific” management.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

ObjectiveTo explore the factors associated with the risk of violent behaviour in inpatients with acute mental disorders， and to provide references for early detection and intervention of violent behaviour in patients with acute mental disorders. MethodsBased on the medical record system of the Affiliated Brain Hospital of Guangzhou Medical University， 1 107 inpatients with acute mental disorders from January to December 2016 were selected， all of whom met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10）. At admission， the risk assessment tools were used to assess the risk level of violent behaviour of inpatients， and 8 variables containing general demographic data and clinical data were selected to explore the factors associated with the risk of violent behaviour in inpatients with acute mental disorders. Thereafter， Logistic regression analysis was performed to screen the factors affecting the high risk of violent behaviour among inpatients. ResultsAmong the 1 107 inpatients with acute mental disorders， 357 （32.25%） patients were at high risk of violence. Regression analysis showed that gender of male （OR=1.747， 95% CI： 1.303~2.342）， manic episodes （OR=2.018， 95% CI： 1.310~3.108） and emergency admission （OR=4.244， 95% CI： 3.083~5.840） were risk factors affecting the high risk of violent behaviour of inpatients. Among different types of mental disorders， patients with depressive disorder had a relatively low risk of violent behaviour （OR=0.397， 95% CI： 0.233~0.677）. ConclusionAmong inpatients with acute mental disorders， patients of emergency admission， being male and manic episodes are more likely to be at high risk of violent behaviour.

Osteoarthritis (OA) is a common chronic degenerative disease, and its condition tends to worsen with age. The pathogenesis of OA is complex, and many risk factors can lead to the occurrence of OA. Iron is one of the essential trace elements in the body, and its metabolic balance is extremely important to human health. Iron overload is closely related to the occurrence and development of OA. Excessive iron deposition in joint tissue can easily lead to lesions of articular cartilage and synovium, as well as affect subchondral bone reconstruction and lead to the occurrence of OA. The author reviewed the relevant research literature in recent years, and reviewed the mechanism of iron overload in the occurrence and development of OA, in order to provide new ideas and directions for the research and diagnosis and treatment of OA.

Objective To investigate the role of peripheral CD14+monocyte-macrophages in the recognition of phosphorylated antigen by γδ T cells and its relationship with treatment outcome. Methods Three kinds of γδ TCR tetramers were used to stain PBMC collected from patients with tuberculosis ( TB) and neonatal umbilical cord blood samples. The proportions of various TB-specific antigen presenting cells (APC) in peripheral blood were analyzed, and their relationships with treatment outcome were assessed based upon clinical data. Results CD14+monocyte-macrophages both in tuberculosis patients′ peripheral blood and neonatal umbilical cord blood were the strongest binding cells to CD277 antibody and γδ TCR tet-ramers. The median (P50) of CD14+monocyte-macrophages reached the highest peak after taking anti-tu-berculosis treatment for about one month and patients′condition was improved obviously during this period. Conclusion This study elucidated that CD14+monocyte-macrophages accounted for the largest proportion of APC when γδ T cells recognized phosphorylated antigens, which provided reference data for further study on the mechanism of γδ T cells restrictively recognizing phosphorylated antigen and their significance in innate and adaptive immunity.

Objective To examine the effects of oxidative stress induced damage to the Prestin expression in HEI-OC1 cells,and to study the mechanism of sensory deafness.Methods We used different concentrations (50μM,100μM,200μM)of hydrogen peroxide canister to cultivate HEI-OC1 cells,and to detect the activity of su-peroxide dismutase(SOD).The quantitative real-time PCR and immunofluorescence were used to detect the prestin expression of mRNA.Results The SOD activity decreased in the HEI-OC1 cells damaged by oxidative stress.The high concentration of the infected group decreased more significantly(F= 9926.293,P<0.01).The expressions of Prestin mRNA and Prestin protein were decreased obviously in the HEI-OC1 cells.The high concentration of in-fected group decreased more significantly (F= 4065.046and7657.217,P<0.01).Conclusion Oxidative stress in-ducing damage inhibits the expression of prestin.Prestin protein may be used as a molecular marker of sensory deafness.

Objective To investigate the relationship between the plasma NT-proBNP level and the severity of acute asthmatic attack,and to provide a reference for the assessment of the severity of asthma and the prognosis of patients with acute asthmatic attack. Methods A total of 103 adult patients with mild,moderate,severe,and very severe acute asthmatic attack were enrolled in this study. The difference of plasma NT-proBNP level among groups,and the correlation between plasma NT-proBNP level and APACHE II score(Acute Physiology and Chron-ic Health Evaluation)were investigated.The correlation between plasma NT-proBNP level and Peak Expiratory Flow (PEF)was also studied in each group. Results There was significant difference in plasma NT-proBNP among groups(P < 0.05). Plasma NT-proBNP and APACHE II score was positive correlated(R = 0.767 1,P < 0.05). However,plasma NT-proBNP was negatively correlated with PEF(R =-0.709 7,P < 0.05). Conclusion NT-proBNP can be used as one of the indexes to evaluate the severity of acute asthmatic attack.