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.

Objective: To investigate the effects of cranial electrotherapy stimulation(CES) with varying parameter configurations on sleep quality in patients diagnosed with chronic insomnia disorder. Methods: Seventy-two participants meeting diagnostic criteria for chronic insomnia disorder were randomly allocated to a four-arm parallel study design.The intervention protocol comprised:Group 1(G1) received CES at 0.5 Hz,300 μA;Group 2(G2) underwent CES treatment at 1.5 Hz,300 μA;Group 3(G3) administered 100 Hz,300 μA stimulation;and Group4(G4) received sham stimulation with identical device placement but no current delivery.Primary outcomes were quantified through polysomnography(PSG) recordings conducted at baseline and post-intervention,whereas secondary outcomes were assessed via standardized sleep questionnaires including the Pittsburgh sleep quality index(PSQI) and Insomnia Severity Index(ISI). Results: Following a 10-day intervention protocol,significant clinical improvements were observed across all active treatment groups(G1-G3) as evidenced by reductions in PSQI.Insomnia severity index(ISI) scores quantitative polysomnographic analysis revealed that both G2(1.5 Hz) and G3(100 Hz) cohorts demonstrated statistically significant enhancements in Flinders Fatigue Scale(FFS) scores,total sleep time(TST),and sleep efficiency(SE),accompanied by reduced sleep onset latency(SOL) compared to baseline measurements.However,no statistically significant differences were detected between the G2 and G3 intervention arms across all measured parameters.CES exerted no significant effect on sleep architecture. Conclusion CES can effectively improve the sleep of patients with chronic insomnia.Within a certain range,a higher frequency of CES leads to better sleep improvement effects.

Objective To explore the association and diagnostic performance of liver imaging reporting and data system(LI-RADS)CT signs with hepatocellular carcinoma(HCC)both in the LI-RADS target population and patients without LI-RADS-defined HCC risk factors.Methods A retrospective analysis was conducted on the data of 435 patients with 482 hepatic lesions confirmed by pathology.Of these,306 cases were assigned to the HCC group(327 HCC lesions),and other 129 cases were assigned to the non-HCC group(77 malignancies and 78 benign lesions).Receiver operating characteristic(ROC)curve analysis assessed the diagnostic performance of LI-RADS v2018 CT signs for HCC,and logistic regression analyses determined the association of CT signs with HCC.Results The asso-ciation of CT signs with all HCC lesions was statistically significant for non-peripheral washout[odds ratio(OR)15.1;95％ confi-dence interval(CI)5.6-40.4;P＜0.01]and non-rim arterial phase hyperenhancement(APHE)(OR 12.4;95％ CI 7.5-20.5;P＜0.01)higher than enhanced capsule(OR 9.9;95％ CI 2.8-34.8;P＜0.01;OR 2.4;95％ CI 1.4-3.8;P=0.01).The sensitivity,specificity,positive predictive value(PPV),and area under the curve(AUC)for diagnosing HCC were 85％,83％,91％,and 0.84,respectively for non-peripheral washout;82％,77％,88％ and 0.79,respectively for non-rim APHE;and 31％,98％,97％ and 0.65,respectively for enhanced capsule.Sensitivity(88％ vs 87％),specificity(83％ vs 82％),PPV(92％ vs 91％)and AUC(0.90 vs 0.87)were all slightly higher when non-peripheral washout,non-rim APHE,enhanced capsule,and ancillary features were combined for the diagnosis of HCC compared to combining the three major features.Enhanced capsule(OR 13.3;95％ CI 3.6-48.9;P＜0.01),blood products in mass(OR 20.3;95％ CI 2.4-171.4;P＜0.01),and mosaic appearance(OR 37.7;95％ CI 4.2-340.0;P＜0.01)were associations with HCC presenting with atypical imaging features and provided high specificity from 98％ to 99％.Conclusion In theLI-RADS target population and patients without LI-RADS-defined HCC risk factors,LI-RADS v2018 CT signs show excellent diag-nostic performance for HCC.Two ancillary features,blood products in mass and mosaic appearance,show good specificity for HCC with atypical imaging features.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

Objective To explore the association and diagnostic performance of liver imaging reporting and data system(LI-RADS)CT signs with hepatocellular carcinoma(HCC)both in the LI-RADS target population and patients without LI-RADS-defined HCC risk factors.Methods A retrospective analysis was conducted on the data of 435 patients with 482 hepatic lesions confirmed by pathology.Of these,306 cases were assigned to the HCC group(327 HCC lesions),and other 129 cases were assigned to the non-HCC group(77 malignancies and 78 benign lesions).Receiver operating characteristic(ROC)curve analysis assessed the diagnostic performance of LI-RADS v2018 CT signs for HCC,and logistic regression analyses determined the association of CT signs with HCC.Results The asso-ciation of CT signs with all HCC lesions was statistically significant for non-peripheral washout[odds ratio(OR)15.1;95％ confi-dence interval(CI)5.6-40.4;P＜0.01]and non-rim arterial phase hyperenhancement(APHE)(OR 12.4;95％ CI 7.5-20.5;P＜0.01)higher than enhanced capsule(OR 9.9;95％ CI 2.8-34.8;P＜0.01;OR 2.4;95％ CI 1.4-3.8;P=0.01).The sensitivity,specificity,positive predictive value(PPV),and area under the curve(AUC)for diagnosing HCC were 85％,83％,91％,and 0.84,respectively for non-peripheral washout;82％,77％,88％ and 0.79,respectively for non-rim APHE;and 31％,98％,97％ and 0.65,respectively for enhanced capsule.Sensitivity(88％ vs 87％),specificity(83％ vs 82％),PPV(92％ vs 91％)and AUC(0.90 vs 0.87)were all slightly higher when non-peripheral washout,non-rim APHE,enhanced capsule,and ancillary features were combined for the diagnosis of HCC compared to combining the three major features.Enhanced capsule(OR 13.3;95％ CI 3.6-48.9;P＜0.01),blood products in mass(OR 20.3;95％ CI 2.4-171.4;P＜0.01),and mosaic appearance(OR 37.7;95％ CI 4.2-340.0;P＜0.01)were associations with HCC presenting with atypical imaging features and provided high specificity from 98％ to 99％.Conclusion In theLI-RADS target population and patients without LI-RADS-defined HCC risk factors,LI-RADS v2018 CT signs show excellent diag-nostic performance for HCC.Two ancillary features,blood products in mass and mosaic appearance,show good specificity for HCC with atypical imaging features.

Objective:To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria ( N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods:The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results:The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion:The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

AIM:To investigate the impact of hippocampal protein phosphatase 1 regulator subunit 17(Ppp1r17)down-regulation on drinking-related behavior in mice,and to explore the protein kinase B(PKB/AKT)/glyco-gen synthase kinase-3β(GSK-3β)/cAMP response element binding protein(CREB)signaling pathway of Ppp1r17 in the development of alcohol dependence.METHODS:Forty male C57BL/6J mice were randomly divided into four groups(n=10):control group,shPpp1r17① group,shPpp1r17② group and shPpp1r17③ group.The mRNA and protein expression levels in the hippocampal tissues were evaluated after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into a control group and a shPpp1r17 group(n=10).An open-field test,conditioned place prefer-ence(CPP)test and righting reflex test were performed.Furthermore,the localization and expression of AAV-shPpp1r17 were detected after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into four groups(n=5):the empty virus+water group,the empty virus+EtOH group,the shPpp1r17+water group and the shPpp1r17+EtOH group.The EtOH group mice drank 9%alcohol continuously for 30 d.The protein expression levels of Ppp1r17,p-AKT,AKT,p-GSK-3β,GSK-3β,p-CREB and CREB were detected by Western blot.RESULTS:(1)The results of qPCR showed that Ppp1r17 was successfully suppressed by shPpp1r17.(2)The behavioral results showed that the shPpp1r17 group mice exhibited enhanced exercise ability and reduced anxiety-like emotions,and the downregulation of Ppp1r17 increased CPP scores and reduced the sensitivity of the mice to alcohol.(3)Immunofluorescence showed that AAV-shPpp1r17 was specifically expressed in the hippocampus.(4)Western blot analysis revealed that Ppp1r17 and the p-AKT/AKT,p-GSK-3β/GSK-3β and p-CREB/CREB ratios were significantly increased after treatment of EtOH.Howev-er,the protein expression of Ppp1r17 was significantly reduced,and the AKT/GSK-3β/CREB pathway was activated after knockdown of Ppp1r17 in the hippocampus.CONCLUSION:Ppp1r17 may suppress CREB phosphorylation through the AKT/GSK-3β/CREB pathway,thereby influencing alcohol drinking preference and locomotor behavior in mice.