eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Objective:To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH).Methods:This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results:Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions:For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95％percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P＜0.001),while MLR in men was significantly higher than that in women(P＜0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-＜60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10％in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.

Objective:To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children.Methods:In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children′s hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed.Results:Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT.Conclusion:L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Purpose To explore the additional value of apparent diffusion coefficient(ADC)histogram in predicting extraprostatic extension(EPE)of prostate cancer.Materials and Methods Consecutive patients undergoing multi-parameter MRI and subsequent radical prostatectomy from January 2021 to December 2022 were retrospectively included in this study.Two radiologists independently estimated EPE by using national cancer institute grading system for extraprostatic extension(EPE grade system),with disagreement resolved by discussion.Histogram metrics were derived from three-dimensional volumes of interest encompassing the entire lesion on ADC maps using FireVoxel,obtaining mean ADC,1st,5th,10th,25th,50th,75th,90th,95th and 99th ADC values.The ADC histograms between the groups with and without EPE were compared.Multivariable Logistic regression analysis was used to identify the independent predictive factors of EPE,and a combined model was developed.Receiver operator characteristic curve was used to evaluate the diagnostic performance,and the area under the curve was calculated and compared.Results Thirty-four patients(34％)had pathologic confirmed EPE after radical prostatectomy.ADC histogram parameters showed significant differences between patients with and without EPE(P＜0.05).Multivariate Logistic regression analysis revealed 99th ADC(OR=0.609,P=0.008)and EPE grade system(OR=4.158,P＜0.001)were independent predictors of EPE.For predicting EPE,the area under the curve of 99th ADC,EPE grade system and the combined model were 0.756,0.805 and 0.856,respectively.The area under the curve of 99th ADC and the EPE grade system in identifying EPE showed no significant difference.The diagnostic efficacy of combined model was significantly superior to that of 99th ADC or EPE grading system(Z=2.223,2.208,both P＜0.05).Conclusion The ADC histogram parameters demonstrate additional value for preoperative prediction of EPE.Combining the 99th ADC histogram parameter with the EPE grade system may improve the diagnostic efficacy of EPE.

Methods: From May 2021 to August 2021, panelists were chosen to collect expert feedback using the modified Delphi method, and 74 spine surgeons from across China agreed to participate. Four rounds were conducted: one in-person meeting and three subsequent survey rounds. Each question received at least 70.0% agreement, indicating a consensus. The grade A, B, and C recommendation were defined as having ≥90.0%, 80.0%–89.9%, and 70.0%–79.9% agreement on each question, respectively. Results: The panelist group consisted of 74 experts, and 72, 70, and 69 questionnaires were collected in three rounds, respectively. In total, 24 questions with 59 options reached consensus after the Delphi rounds, including indications (adjacent vertebral diseases after lumbar internal fixation) and contraindications (previous surgery or bone destructive diseases lead to the destruction or absence of bone in the lamina or isthmus); advantages (intraoperative traction of paravertebral soft tissue is small) and disadvantages (not three-column fixation.); preoperative evaluation; complications; and postoperative follow-up evaluation, of CBT. Conclusions The modified Delphi method achieved expert consensus on the clinical use of CBT for lumbar pedicle screws. This consensus document establishes clear guidelines for indications, contraindications, surgical techniques, and postoperative management, thereby enhancing clinical decision-making and promoting the safe and effective use of CBT. While the initial study focused on Chinese surgeons, future research will seek to validate and expand these findings from a broader international perspective.

Objective: To investigate the expression and molecular mechanism of dickkopf 1 ( DKK1 ) in tongue squamous cell carcinoma (TSCC) by bioinformatics method and molecular biology experiments． Methods: The patients information wasdownload from TCGA-TSCC database，the differentially expressed genes between the cancer and normal tissues were screened by NetworkAnalysed site，the key genes and clinical prognosis were identified through Kaplan-Meier analysis and Lasson regression，the functions and pathways of differentially expressed genes were gained by GO and KEGG database，the expression of DKK1 mRNA and protein in TSCC as well as its relationship with clinicopathological features were analyzed by UALCAN database and immunohistochemistry．Western blot assay was conducted to detect the protein expression of DKK1 in TSCC cells，and siRNA was used to konck down the expression of DKK1 protein in Cal27 cells. Results : The three key genes DKK1，CYP19A1 and IRX4， which were highly expressed in tongue squamous cell carcinoma and the survival rate of TSCC patients with high expression group was poor，were screened through NetworkAnalysed ，Kaplan-Meier analysis and Lasson regression method．UALCAN database showed that the mRNA level of DKK1 in TSCC tissues was higher than that in normal tissues，and its high expression was significantly correlated with clinical stage，histological grade and lymph node metastasis of TSCC patients．The immunohistochemistry assay suggested that the positive rate of DKK1 protein in clinical stage Ⅲ + Ⅳ TSCC tissues was significantly higher than that in stage Ⅰ + Ⅱ TSCC tissues．In addition， the expression level of DKK1 protein in TSCC tissues was significantly higher than that in adjacent tissues．Western blot assay also showed that the protein expression of DKK1 in TSCC cell Cal27 was much higher than normal oral epithelial cell HOEC．When knock down the protein expression of DKK1 in Cal27，the expression of β-catenin、p- p65 和 p65 werealso reduced． Conclusion DKK1 is highly expressed in tongue squamous cell carcinoma tissues and cells and plays an important role．It may be a new target for early diagnosis and drug treatment of TSCC.