Objective: To investigate and analyze the IgM/IgG antibody titer levels and population characteristics of local type O blood donors, and to provide data support for the establishment of a low-titer group O blood donor bank. Methods: Whole blood samples were collected from 527 type O blood donors. The agglutination of IgM and IgG anti-A/anti-B antibodies at titers 64 and 128 was assessed using an enzyme immunoassay reader. The distribution of antibody agglutination was displayed using GraphPad Prism 9.5. Statistical analysis was performed to compare antibody agglutination differences among donors of different genders, age groups, and donation frequencies. Results: At a titer of 64, the non-agglutination rate of IgM anti-A/anti-B was 71.35%, and that of IgG anti-A/anti-B was 54.46%. At a titer of 128, the non-agglutination rate of IgM anti-A/anti-B was 83.68%, and that of IgG anti-A/anti-B was 70.21%. At a titer of 64, the agglutination rate of IgM anti-B was significantly higher in female donors than in male donors (23.08% vs 13.71%, P<0.05). The agglutination rates of IgM anti-A/anti-B at a titer of 64 decreased with age in different age groups (anti-A: 26.22% vs 18.28% vs 8.49%; anti-B: 19.82% vs 11.83% vs 5.66%, P<0.05). The agglutination rates of IgM anti-A/anti-B at a titer of 64 were both higher in first-time donors than in repeat donors (anti-A: 24.00% vs 15.82%; anti-B: 18.00% vs 10.73%, P<0.05). The agglutination rate of IgG anti-A at a titer of 128 was higher in first-time donors than in repeat donors (26.57% vs 6.21%, P<0.05). Conclusion: The establishment of a low-titer type O whole blood donor bank should primarily target males, donors aged>30 years and repeat donors, with both IgM and IgG antibodies included in the antibody testing scope.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Advanced radiotherapy technology enables the dose to more accurately conform to the tumor target area of the patient, providing accurate treatment for the patient, but the gradient of the patient's radiation dose at the tumor edge is getting larger, which putting forward higher requirements for radiotherapy dose verification. The dose verification system software KylinRay-Dose4D can verify the patient's pre-treatment plan and the in vivo/on-line dose during the patient's treatment, providing important reference for the physicist to modify the radiotherapy plan and ensuring that the patient receives accurate treatment. This study introduces the overall design and key technologies of KylinRay-Dose4D, and tests the pre-treatment plan dose checking calculation and 2D/3D dose verification through clinical cases. The test results showed that the 2D/3D gamma pass rate (3 mm/3%) of KylinRay-Dose4D reconstructed dose compared with TPS plan dose and measured dose is larger than 95%, which indicating that the reconstructed dose of KylinRay-Dose4D meets the requirement of clinical application.
Humans ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy, Intensity-Modulated/methods* ; Software ; Neoplasms ; Phantoms, Imaging ; Radiometry/methods*

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

Objective : Cas9-RNP biomimetic nanoparticles cas9-RNP@ MMs were prepared by encapsulating the Cas9 Ribonucleoprotein complex (RNP) using mouse macrophage membranes，with the aim of utilizing this biomimetic nanoparticle to deliver the Cas9-RNP complex for gene editing ，and further study the endocytosis of Cas9- RNP@ MMs and its gene editing effect in mouse macrophage RAW264. 7 in vitro ，providing evidence for the development oflow-toxicity biomimetic nanoparticle carriers that inhibit NLRP3 therapeutic targets． Methods : The purified mouse macrophage membrane was mixed with the prepared cas9-RNP mixture，and after ultrasound，the CAS9- RNP@ MMS was obtained by liposome extrusion instrument ; The particle size of Cas9-RNP@ MMswas measured by nanoparticle tracking analysis，and the particle morphology of Cas9-RNP@ MMs was observed under transmission electron microscope．Laser confocal Fluorescence microscope imaging was used to analyze the endocytosis Cas9-RNP @ MMs．The Biocompatibility of Cas9-RNP@ MMs was measured by MTT assay．The expression of NLRP3 was detected by qPCR and Western blot to verify the knockdown effect of Cas9-RNP@ MMs on NLRP3 gene. Results: The average particle diameter of Cas9-RNP@ MMs prepared from macrophages was about 216 nm．Under laser confocal fluorescence microscope，the Cas9-RNP@ MMs could be successfully endocysed by Raw246. 7 cell．MTT assay indicated that the Cas9-RNP@ MMs-treated mouse macrophage RAW246. 7 had good biocompatibility．qPCR and Western blot showed that two NLRP3-specific guide RNA were mediated by Cas9-RNP@ MMs，with good effect of knockdown NLRP3 gene expression． Conclusion Nano-scale vesicles Cas9-RNP@ MMs loaded with Cas9-RNP complexes were successfully prepared by biomimetic nanoparticles． Cas9-RNP@ MMs have good biocompatibility and can be efficiently endocytosed by RAW246. 7 cells．Cas9-RNP@ MMs containing NLRP3-specific sgRNA can specifically knock down NLRP3 gene expression.

Objective:To systematically evaluate the efficacy and safety of obinutuzumab-based regimen versus rituximab-based regimen in treatment of B-cell non-Hodgkin lymphoma (B-NHL).Methods:The Cochrane clinical controlled trials database, PubMed, Embase, American Society of Hematology meeting proceedings, American Society of Clinical Oncology annual meeting proceedings and ClinicalTrails database were searched for studies on the use of regimens containing obinutuzumab or rituximab for the treatment of B-NHL. Patients were divided into obinutuzumab group and rituximab group according to their medication status. Review Manager 5.3 software was used to compare the efficacy and safety of the two groups.Results:A total of 7 randomized controlled trials were selected, including 4 235 patients (1 430 cases of follicular lymphoma, 2 102 cases of diffuse large B-cell lymphoma, and 703 cases of other B-NHL); 2 121 cases were in the obinutuzumab group and 2 114 cases were in the rituximab group. Among 4 162 patients who could be evaluated, the objective response rate (ORR) in the obinutuzumab group was higher than that in the rituximab group [75.1% (1 565/2 083) vs. 72.7% (1 512/2 079); OR = 1.19, 95% CI 1.01-1.41, P = 0.03]. Progression-free survival (PFS) in the obinutuzumab group was better than that in the rituximab group ( HR = 0.86, 95% CI 0.75-0.99, P = 0.03). Among 3 542 patients who could be evaluated for adverse reactions, the incidence of grade 3-4 adverse reactions in the otuzumab group was higher than that in the rituximab group [61.8% (1 098/ 1 776) vs. 54.2% (958/1 766); OR = 1.50, 95% CI 1.29-1.74, P < 0.001], the incidence of grade 3-4 infusive-related adverse reactions [7.5% (158/1 776) vs. 3.1% (65/1 766); OR = 2.56, 95% CI 1.91-3.45, P < 0.001] and neutropenia [34.1% (597/1 749) vs. 29.4% (511/1 738); OR = 1.27, 95% CI 1.09-1.47, P = 0.002] in the obinutuzumab group were higher than those in the rituximab group. Conclusions:The ORR and PFS of B-NHL patients treated with obinutuzumab-based regimen are better than those treated with rituximab-based regimen, but the influence of adverse reactions should be considered when selecting the regimen.

MicroRNAs(miRNAs)are trans-acting small regulatory RNAs that work coordinately with transcription factors(TFs)to shape the repertoire of cellular mRNAs available for translation.Despite our growing knowledge of individual plant miRNAs,their global roles in gene regulatory networks remain mostly unassessed.Based on interactions obtained from public databases and curated from the literature,we reconstructed an integrated miRNA network in Arabidopsis that includes 66 core TFs,318 miRNAs,and 1712 downstream genes.We found that miRNAs occupy distinct niches and enrich miRNA-containing feed-forward loops(FFLs),particularly those with miRNAs as intermediate nodes.Further analyses revealed that miRNA-containing FFLs coordi-nate TFs located in different hierarchical layers and that intertwined miRNA-containing FFLs are associated with party and date miRNA hubs.Using the date hub MIR858A as an example,we performed detailed molecular and genetic analyses of three interconnected miRNA-containing FFLs.These analyses revealed individual functions of the selected miRNA-containing FFLs and elucidated how the date hub miRNA fulfills multiple regulatory roles.Collectively,our findings highlight the prevalence and importance of miRNA-containing FFLs,and provide new insights into the design principles and control logics of miRNA regulatory networks governing gene expression programs in plants.

Objective: To investigate the effects of miR-124a on proliferation, migration and invasion in rheumatoid arthritis synovial fibroblasts (RASFs) and the underlying mechanisms. Methods: RASFs were isolated and cultured from synovial tissue, then qRT-PCR was used to detect the levels of AKT2 mRNA and miR-124a in RASFs. Western blot was applied to determin the expression level of AKT2 protein. RASFs were transfected with miR-124a, anti-miR-124a, si-AKT2 or pcDNA-AKT2 to up-regulate or down-regulate the expression level of miR-124a or AKT2 protein. The cells were divided into normal group of normal synovial tissue, control NC group, miR-con group, miR-124a group, si-con group, si-AKT2 group, miR-124a+pcDNA group and miR-124a+pcDNA-AKT2 group. MTT assay was carried out to measure the proliferation of RASFs. Transwell assay was carried out to detect the migration and invasion cell number of RASFs. Dual-luciferase reporter assay system was implemented to verify the relationship between miR-124a and AKT2. Independent sample t-test and one way analysis of variance (ANOVA) test (square deviation) were used for statistical analysis. Results: ① Compared with normal group, the expression of miR-124a (0.92±0.19) decreased significantly (t=5.788, P<0.01), AKT2 mRNA (3.15±0.63) increased significantly (t=-3.486, P=0.025), AKT2 protein (2.09±0.64) increased significantly (t=-2.959, P=0.042). ② Ccompared with NC group and miR-con group, miR-124a expression (4.17±0.46) increased significantly (F=131.830, P<0.01), migration cell number (34±6) decreased significantly, invasion cell number (14.5±3.1) decreased significantly (F₁=35.788, F₂=27.211, P<0.01). ③ Compared with mir-con group (1.02±0.18), WT-AKT2 in miR-124a group showed a significant decrease in its relative activity (0.31±0.11) (t=5.830, P<0.01). ④ Compared with NC group and si-con group, the expression of AKT2 protein (0.97±0.03) in si-AKT2 group decreased significantly (F=128.056, P<0.01), the number of migrating cells (32±4), and the number of invasive cells (18.6±2.2) (F₁=-70.082, F₂=36.524, P<0.01) were decreased significantly. ⑤ Compared with miR-con group, AKT2 protein expression in miR-124a group decreased significantly (0.21±0.03); compared with miR-124a+pcDNA group, AKT2 protein expression in miR-124a+pcDNA-AKT2 group was increased significantly (F=52.487, P<0.01). ⑥ Compared with miR-con group, the number of RASFs migrating cells (30±5) and invasive cells (12.5±1.8) in miR-124a group were significantly decreased; compared with miR-124a+pcDNA group, the number of RASFs migrating cells (71±4) and invasive cells (26.4±4.5) in miR-124a+pcDNA-AKT2 group were significantly increased (F₁=30.957, F₂=49.960, P<0.01). Conclusion MiR-124a can inhibite the proliferation, migration and invasion of RASFs by targeting AKT2 gene. MiR-124a is expected as a molecular target for diagnosis and treatment of rheumatoid arthritis.