Objective:To analyze the serological and molecular characteristics of rare A el and B el subtypes in the ABO blood group system, and to explore their genotype-phenotype correlation and the potential clinical significance. Methods:From January 1st, 2021, to January 1st, 2025, 289, 815 samples subjected to ABO blood grouping in Henan Provincial People′s Hospital were selected. Samples demonstrating discrepancies between forward and reverse typing, or consistent typing but with abnormal agglutination degree were included. Those affected by underlying diseases, transplantation, age-related and other interferences were excluded. A total of 169 suspected ABO subgroup samples were identified. Sanger sequencing of exons 1-7 and relevant regulatory regions of the ABO gene was performed. Protein structure modeling and mutation effect analysis for two'el′ subtype glycosyltransferases (GTs) were conducted using SWISS-MODEL and PyMOL.Results:A total of 12 Ael, 6 B el, and 2 AB el subtypes were identified. Serological analysis revealed that all 18 A el/B el samples exhibited O phenotype in forward typing. Among them, A el subtypes showed weaker agglutination in reverse typing with A 1c than with Bc (>2+), while the opposite pattern was observed in B el subtypes. The two AB el samples were typed as A in forward typing, with agglutination ranging from 0-1+with Bc in reverse typing. Genetic analysis indicated that AEL.02 (c.646T>A, p.Phe216Ile) was the predominant allele in A el samples accounting for 7 cases. Also, we found an AEL.02-like variant (lacking c.681G>A), AEL.10 (c.963insC), and carrying a compound variant of c.322C>T (p.Gln108Ter) and c.296C>T (p.Thr99Ile). Among B el samples, BEL.03 (c.502C>T, p.Arg168Trp) accounted for 4 cases, one of which lacked the c.297A>G mutation, and novel mutations such as c.145_146dupCG were detected. Structural simulation demonstrated that AEL.02 and BEL.03 disrupted the hydrogen-bonding network within the active centers of GTA and GTB, respectively, and these mutations probably significantly impaired the structural stability of the corresponding GTs. Additionally, the c.296C>T mutation also markedly affected GTA structural stability. Conclusion:A el/B el subtypes are prone to mis-identify routine blood types. Their molecular mechanisms involved a variety of functional variantions, and integrating molecular detection is crucial for achieving accurate sub-typing and transfusion safety.

Objective To review the research of safe injection protocols for peripheral norepinephrine(pNE),to make clear the main contents of safe injection protocols and the compliance of clinical implementation protocols,and to provide reference for clinical nurses to use drugs safely.Methods Systematic searches were conducted in the PubMed database,the Embase database from the Netherlands,the Web of Science,the Cochrane library,CNKI,Wanfang database,VIP,and the China biomedical literature database for studies related to safe injection protocols for pNE.The search period extended from the establishment of the databases to April 30,2024.Two researchers conducted data extraction and summary analysis of the included literature.Results A total of 10 articles were incorporated,including 2 guidelines,4 observational retrospective cohort studies,2 observational prospective cohort studies,2 ambispective cohort study.All documents provide a complete safe injection scheme of pNE,and its main contents were as follows:the drug concentration should be diluted to 8～64 mg/L;the injection dose should be small,and the maximum dose should not exceed 0.5 μg·kg-1·min-1 or 25 μg/min;a short infusion time was appropriate,among which 4 schemes require≤24 hours;intravenous catheters should be large-bore models,mainly 16,18 and 20 G;selection of infusion sites with favorable venous conditions of upper limb should be selected for injection;during infusion,regular and effective monitoring was required,and the frequency of monitoring should be once an hour,not exceeding a maximum of 2 hours;observation of the puncture site,and must assess whether there was blood return to the venous pathway,develop an emergency plan for drug extravasation.Several studies provided the compliance analysis of the protocol.The items with the highest compliance were using the drug concentration specified in the protocol,with the highest implementation rate of 100.0%.The items with low compliance were:using ultrasonic catheterization or evaluation,with minimum 26.6%;monitor according to the specified time frequency,with a minimum of 36.0%;selection of infusion sites,with a minimum of 65.0%.Conclusion The pNE is safe and feasible in emergency situations,but it comes with numerous risks and limitations.Norepinephrine(NE)should be administered at low concentrations and small doses,using large-caliber venous indwelling needles,and choosing optimal injection sites.Ultrasound assessment and localization can be used if conditions permit.Short-term infusion is preferred,and effective monitoring should be conducted at regular intervals during the infusion.Emergency plans for drug extravasation should be established.Developing safe injection protocols can reduce the incidence of adverse events such as extravasation.

Objective To review the research of safe injection protocols for peripheral norepinephrine(pNE),to make clear the main contents of safe injection protocols and the compliance of clinical implementation protocols,and to provide reference for clinical nurses to use drugs safely.Methods Systematic searches were conducted in the PubMed database,the Embase database from the Netherlands,the Web of Science,the Cochrane library,CNKI,Wanfang database,VIP,and the China biomedical literature database for studies related to safe injection protocols for pNE.The search period extended from the establishment of the databases to April 30,2024.Two researchers conducted data extraction and summary analysis of the included literature.Results A total of 10 articles were incorporated,including 2 guidelines,4 observational retrospective cohort studies,2 observational prospective cohort studies,2 ambispective cohort study.All documents provide a complete safe injection scheme of pNE,and its main contents were as follows:the drug concentration should be diluted to 8～64 mg/L;the injection dose should be small,and the maximum dose should not exceed 0.5 μg·kg-1·min-1 or 25 μg/min;a short infusion time was appropriate,among which 4 schemes require≤24 hours;intravenous catheters should be large-bore models,mainly 16,18 and 20 G;selection of infusion sites with favorable venous conditions of upper limb should be selected for injection;during infusion,regular and effective monitoring was required,and the frequency of monitoring should be once an hour,not exceeding a maximum of 2 hours;observation of the puncture site,and must assess whether there was blood return to the venous pathway,develop an emergency plan for drug extravasation.Several studies provided the compliance analysis of the protocol.The items with the highest compliance were using the drug concentration specified in the protocol,with the highest implementation rate of 100.0%.The items with low compliance were:using ultrasonic catheterization or evaluation,with minimum 26.6%;monitor according to the specified time frequency,with a minimum of 36.0%;selection of infusion sites,with a minimum of 65.0%.Conclusion The pNE is safe and feasible in emergency situations,but it comes with numerous risks and limitations.Norepinephrine(NE)should be administered at low concentrations and small doses,using large-caliber venous indwelling needles,and choosing optimal injection sites.Ultrasound assessment and localization can be used if conditions permit.Short-term infusion is preferred,and effective monitoring should be conducted at regular intervals during the infusion.Emergency plans for drug extravasation should be established.Developing safe injection protocols can reduce the incidence of adverse events such as extravasation.

Objective:To analyze the serological and molecular characteristics of rare A el and B el subtypes in the ABO blood group system, and to explore their genotype-phenotype correlation and the potential clinical significance. Methods:From January 1st, 2021, to January 1st, 2025, 289, 815 samples subjected to ABO blood grouping in Henan Provincial People′s Hospital were selected. Samples demonstrating discrepancies between forward and reverse typing, or consistent typing but with abnormal agglutination degree were included. Those affected by underlying diseases, transplantation, age-related and other interferences were excluded. A total of 169 suspected ABO subgroup samples were identified. Sanger sequencing of exons 1-7 and relevant regulatory regions of the ABO gene was performed. Protein structure modeling and mutation effect analysis for two'el′ subtype glycosyltransferases (GTs) were conducted using SWISS-MODEL and PyMOL.Results:A total of 12 Ael, 6 B el, and 2 AB el subtypes were identified. Serological analysis revealed that all 18 A el/B el samples exhibited O phenotype in forward typing. Among them, A el subtypes showed weaker agglutination in reverse typing with A 1c than with Bc (>2+), while the opposite pattern was observed in B el subtypes. The two AB el samples were typed as A in forward typing, with agglutination ranging from 0-1+with Bc in reverse typing. Genetic analysis indicated that AEL.02 (c.646T>A, p.Phe216Ile) was the predominant allele in A el samples accounting for 7 cases. Also, we found an AEL.02-like variant (lacking c.681G>A), AEL.10 (c.963insC), and carrying a compound variant of c.322C>T (p.Gln108Ter) and c.296C>T (p.Thr99Ile). Among B el samples, BEL.03 (c.502C>T, p.Arg168Trp) accounted for 4 cases, one of which lacked the c.297A>G mutation, and novel mutations such as c.145_146dupCG were detected. Structural simulation demonstrated that AEL.02 and BEL.03 disrupted the hydrogen-bonding network within the active centers of GTA and GTB, respectively, and these mutations probably significantly impaired the structural stability of the corresponding GTs. Additionally, the c.296C>T mutation also markedly affected GTA structural stability. Conclusion:A el/B el subtypes are prone to mis-identify routine blood types. Their molecular mechanisms involved a variety of functional variantions, and integrating molecular detection is crucial for achieving accurate sub-typing and transfusion safety.

The use of tyrosine kinase inhibitors （TKI） has been an important advance in the systemic treatment of hepatocellular carcinoma， but their sustained anti-angiogenic therapy leads to increased tumor hypoxia， accelerates the development of a hypoxic microenvironment and promotes the expressions of hypoxia-inducible factors （HIF）， thereby inducing drug resistance of tumor patients to TKI. This paper summarizes the mechanism of action of HIF mediating TKI resistance in hepatocellular carcinoma in aspects of metabolic reprogramming， abnormal expressions of cancer and cancer-associated genes， and ferroptosis， and sorts resistance response strategies to provide reference for clinical solutions to TKI resistance issues. As results show， HIF/ glycolysis axis inhibitors （isoflavonoid genistein， simvastatin， etc.） can improve TKI resistance based on metabolic reprogramming mechanism； oncogene-targeted inhibitors combined with TKI （the combination of capsaicin and sorafenib） can improve TKI resistance based on abnormal expression of cancer and cancer-related genes； fatty acid synthase inhibitor （orlistat） can improve TKI resistance based on ferroptosis mechanism.

Objective To investigate the effect of computer-aided diagnosis(CAD)as a"second reader"integrated in prostate cancer(PCa)multiparametric magnetic resonance imaging(mpMRI)on the diagnostic performance.Methods Sixty-four patients were recruited retrospectively.Six readers were divided into 3 groups according to the experience.Unknown the pathologic diagnosis,readers graded according to prostate imaging reporting and data system(PI-RADS)v2.1 and accepted or rejected the revision of PI-RADS v2.1 scores by CAD.Using pathology as the gold standard,the diagnostic efficiency,diagnostic confidence and reading time of PI-RADS v2.1 were compared before and after CAD assistant.Results On the level of lesions,without CAD,the area under the curve(AUC)of reader A1 was higher than B1,C1 and C2,and the AUC of reader A2 was higher than C1 and C2,the difference was statistically significant(P＜0.05).While the difference of AUC among other readers were not significant(P＞0.05).With CAD,the difference of AUC among all readers were not significant(P＞0.05).On the level of patients,the mean AUC of all readers with CAD[0.903,95％confidence interval(CI)0.848-0.958]was higher than that without CAD(0.863,95％CI 0.800-0.929),the differ-ence was statistically significant(F=6.52,P=0.040).The difference of AUC between without and with CAD assistance was-0.040(95％CI-0.078--0.003),standard deviation was 0.016,the difference was statistically significant(t=-2.55,P=0.040).The diag-nostic confidence of readers was improved significantly with CAD(P＜0.05).Besides,the average reading time of each case required an additional 0.8 min.Conclusion After integrating CAD into PCa mpMRI diagnosis as a"second reader",the performance of less experienced readers can be improved and show similar diagnostic efficiency with experienced readers.

The pathophysiology of depressive disorder is complex. However, the understanding of its pathogenesis is still relatively limited in previous studies. In recent years, the neuroimmune mechanism has received extensive attention. The bidirectional communication between the central nervous system and the peripheral immune system has been identified to play an important role in depressive disorder. This article reviews the research progress of neuroimmune response in patients with depressive disorders and animal models of depression to raise considerations for the treatment of depressive disorder.

The pathophysiology of depressive disorder is complex. However, the understanding of its pathogenesis is still relatively limited in previous studies. In recent years, the neuroimmune mechanism has received extensive attention. The bidirectional communication between the central nervous system and the peripheral immune system has been identified to play an important role in depressive disorder. This article reviews the research progress of neuroimmune response in patients with depressive disorders and animal models of depression to raise considerations for the treatment of depressive disorder.

Objective To evaluate the influence of stress distributions on bone-anchored maxillary protraction at different protraction sites, so as to guide patients to choose an optimal protraction site in clinic. Methods A three-dimensional (3D) finite element model of child head with implant anchorages was establised. Four protraction sites were set according to the position of implant installation. Working condition 1: the alveolar bone at the intersection of distal 2 mm of primary lateral incisor crown distal surface and gingival cervical margin to 5 mm. Working condition 2: the alveolar bone at the intersection of mesial 2 mm of maxillary first primary molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 3: the alveolar bone at the intersection of mesial 2 mm of maxillary first molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 4: the alveolar bone at the intersection of distal 2 mm of maxillary first molar crown distal surface and gingival cervical margin to 5 mm. The finite element models were loaded with 500 g protraction force at each side with 30° forward direction to the occlusal plane. Stress distributions on each suture were analysed. Results The maximum stress of frontomaxillary suture was in working condition 2 (1 477-28 190 Pa). The maximum stress of nasomaxillary suture was in working condition 1 (5.296-924 Pa). The maximum stress of zygomaticomaxillary suture was in working condition 4(394.7-13 130 Pa). The maximum stress of zygomaticofrontalis suture was in working condition 4 (495.2-31 690 Pa). The maximum stress of zygomaticotemporal suture was in working condition 3 (1 148-15 870 Pa). The maximum stress of medianpalatine suture was in working condition I (6.479-730 Pa). Conclusions When the protraction sites are set in distal maxillary primary lateral incisor and mesial maxillary first primary molar, it is of positive significance to improve the concave profile, especially in nose root. When the protraction sites are set in mesial or distal maxillary first molar, it is of positive significance to improve the concave profile, especially in maxillary basal bone of the midface.

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.