ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

OBJECTIVE To analyze the distribution of the nasopharyngeal microbiota in children with refractory chronic sinusitis and adenoid hypertrophy using 16S rRNA next-generation high-throughput sequencing technology,and to compare the effects of adenoidectomy on the nasopharyngeal microbiota in such patients,with the aim of providing microbiological evidence for the clinical treatment of refractory chronic sinusitis with adenoid hypertrophy.METHODS Children diagnosed with chronic sinusitis with adenoid hypertrophy who visited Chengdu Women and Children's Central Hospital from January 2024 to March 2025 and whose symptoms were not controlled after drug treatment were selected.They were divided into a non-surgical group and a surgical group based on whether they underwent adenoidectomy.The VAS scores,Lund-Kennedy scores,and microbial community detection rates between the two groups were compared.RESULTS The final VAS scores and Lund-Kennedy scores for surgical group were both lower than those for non-surgical group,with statistically significant differences(tVAS score=3.491,P<0.001;tLund-Kennedy score=4.166,P<0.001).Comparisons of microbial α diversity analysis and β diversity at the phylum and genus levels between the two groups showed no statistically significant differences(tα diversity analysis=0.524,P=0.604;Rβ diversity at the phylum level=0.075,P=0.454;Rthe genus level=0.117,P=0.538).The dominant bacterial groups at the phylum level were the same in both groups,including Proteobacteria,Bacillales,Actinobacteria,Bacteroidetes,and Firmicutes,but the average relative abundance differed between the two groups.Species comparison analysis showed that at the phylum level,the abundance of Proteobacteria and Thermodesulfovibrio in surgical group was higher than that in non-surgical group;At the genus level,the abundance of the genus Moraxella was higher in non-surgical group than in surgical group,while the abundance of the genera Acidovorax,Stenotrophomonas,Delftia,Burkholderia,Caballeronia,Paraburkholderia,Lactobacillus,Devosia,norank_f_Muribaculaceae,Paracoccus,and Kocuria was lower in non-surgical group than in surgical group.CONCLUSION Children with refractory sinusitis and adenoid hypertrophy all have rich microbial communities in the nasopharynx.Adenoid surgery has no significant effect on the diversity of the nasopharyngeal microbial community.However,the composition of the microbial community has changed,and there are significant species differences,which may be related to the resolution of local obstruction after adenoidectomy and changes in the survival environment of the nasopharyngeal microbial community.

Objective:To compare the differences of long-term survival rates between hemodialysis (HD) and peritoneal dialysis (PD) in the oldest old end-stage renal disease (ESRD) patients, and analyze the influencing factors of mortality.Methods:It was a retrospective cohort study. The clinical data from the oldest old patients (≥80 years old) who underwent HD or PD for the first time and maintained dialysis treatment for ≥3 months in the Zhejiang Dialysis Registration System from January 1, 2008 to December 31, 2021 were collected. The follow-up endpoint was until the patients' death or December 31, 2022. The propensity score matching method was used to match groups. Kaplan-Meier method and log-rank test were used to compare the differences of long-term survival rates between the two groups. Cox regression analysis was used to analyze the risk factors of mortality.Results:A total of 5 880 the oldest old dialysis patients were included in this study, with 5 363 patients in the initial HD group and 517 patients in the initial PD group. After matching, there were 517 patients in the HD group and 517 patients in the PD group. The median survival time of HD group before matching was 39.9 months, with 1-year, 3-year, and 5-year survival rates of 85.4%, 54.9%, and 30.0%, respectively. The median survival time of PD group was 32.9 months, with 1-year, 3-year, and 5-year survival rates of 82.5%, 47.1%, and 22.3%, respectively. After matching, the median survival time of HD group was 40.3 months, and the 1-year, 3-year, and 5-year survival rates were 86.1%, 57.8%, and 29.1%, respectively. The survival rate of PD group remained unchanged. The difference of 1-year survival rate between the two groups was not statistically significant, but the 2-year, 3-year, 4-year, 5-year, and overall survival rates in HD group were higher than those in PD group (Log‐rank test, χ2=4.897, P=0.027; χ2=9.693, P=0.002; χ2=10.194, P=0.001; χ2=7.868, P=0.005; χ2=12.510, P<0.001). Multivariate Cox regression analysis showed that HD (HD/PD, HR=0.794, 95% CI 0.669-0.943, P=0.009), increasing age ( HR=1.069, 95% CI 1.038-1.110, P<0.001), comorbidity with chronic obstructive pulmonary disease ( HR=1.510, 95% CI 1.065-2.139, P=0.021) and serum albumin <35 g/L ( HR=1.393, 95% CI 1.165-1.665, P<0.001) were independent correlated factors of mortality. Conclusions:There is no significant difference in the 1-year survival rate between HD and PD groups. The survival rate for more than 1 year in HD patients is higher than that in PD patients. HD is an independent protective factor of survival, and increasing age, comorbidities of chronic obstructive pulmonary disease, and serum albumin <35 g/L are independent risk factors affecting the survival in the oldest old dialysis patients.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective To investigate how culture duration affects the expression of immune membrane proteins in human monocyte-derived dendritic cells (DCs) and their exosomes (DEXs). Methods Human monocytes were induced with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to differentiate into DCs and were subsequently matured with tumor necrosis factor α(TNF-α). Exosomes were isolated by ultracentrifugation, and DEXs were identified by transmission electron microscopy and Amnis imaging flow cytometry, which were also used to quantify the expression of immune membrane proteins on DCs and DEXs. Results On the 10th day of culture, DCs displayed high surface expression of CD11c, CD80, CD86, major histocompatibility complex class I (MHC-I), and MHC-II. Expression peaked at day 18(CD11c: 78.66%±20.33%, CD80: 76.41%±10.02%, CD86: 96.43%±0.43%, MHC-I: 84.71%±2.96%, MHC-II: 80.01%±7.03%). After day 24, the overall expression showed a declining trend, with statistically significant differences observed for all markers except CD80 and MHC-II. By day 30, 80% of the DCs still expressed CD80, CD86, and MHC-II. The expression of immune membrane proteins on DEX surfaces also reached its peak on day 18, followed by an overall decline with prolonged culture time, with statistically significant differences observed for all markers except CD80. Correlation analysis revealed a significant positive relationship between the expression levels of immune membrane proteins on DC and DEX surfaces (CD11c: r=0.98; CD80: r=0.65; CD86: r=0.82; MHC-I: r=0.86; MHC-II: r=0.93). Conclusion Human monocyte-derived DCs in vitro express high expression of immune membrane proteins and maintain stable expression over a specific period. The exosomes secreted by these cells similarly demonstrate high surface expression of immune membrane proteins, with temporal trends aligned with those of the parent DCs.
Humans ; Dendritic Cells/immunology* ; Exosomes/immunology* ; Monocytes/metabolism* ; Cells, Cultured ; Time Factors ; B7-1 Antigen/metabolism* ; Membrane Proteins/immunology* ; Cell Culture Techniques/methods* ; B7-2 Antigen/metabolism* ; Cell Differentiation ; CD11c Antigen/metabolism* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology*

Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of patients with adrenal diffuse large B-cell lymphoma(DLBCL).Methods·From March 2002 to December 2022,a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival outcomes,and prognostic factors.Patients'gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes.Results·The median age of the patients was 62(15?82)years and the male-to-female ratio was 2.3∶1.Among them,63 patients(60.0%)were over 60 years old,22 patients(21.0%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or higher,87 patients(82.9%)were staged Ann Arbor Ⅲ?Ⅳ,92 patients(87.6%)had elevated serum lactate dehydrogenase(LDH)levels(above the upper limit of reference),84 patients(80.0%)had extranodal invasion in at least two organs,67 patients(63.8%)were of non-germinal center B-cell(non-GCB)origin,and 95 patients(90.5%)had an international prognosis index(IPI)scored over 2.With a median follow-up of 28.3(0.7?191.9)months,the estimated 2-year overall survival(OS)rate and progression-free survival(PFS)rate were 68.3%and 53.1%,respectively.The estimated 5-year OS rate and PFS rate were 52.6%and 44.0%,respectively.Among 93 patients who could be evaluated for clinical outcomes,62(66.7%)got a complete response(CR).Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS,and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS.Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D(KMT2D;n=17,37%),Pim-1 proto-oncogene,serine/threonine kinase(PIM1;n=17,37%),MYD88 innate immune signal transduction adaptor(MYD88;n=15,33%),CD79b molecule(CD79B;n=13,28%),and BTG anti-proliferation factor 2(BTG2;n=10,22%).Conclusion·Age over 60 years is an adverse prognostic factor for PFS,and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL.Patients exhibited high frequencies of KMT2D,PIM1,MYD88,CD79B,and BTG2 mutations,as well as an increased proportion of the MCD-like subtype.

Objective·To investigate the clinicopathologic features,gene mutation profile,and real-world survival prognosis of diffuse large B-cell lymphoma(DLBCL)with pulmonary involvement.Methods·The clinical data of 110 patients with newly diagnosed,pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between August 2003 and December 2022 were retrospectively collected and analyzed.Evaluation of the efficacy of treatment,survival analyses,and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide,doxorubicin/epirubicine,vincristine,and prednisone(R-CHOP).A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations.Results·Among the 110 patients,72(65.5%)were>60 years old,52(47.3%)were female,92(83.6%)presented with Ann Arbor stage Ⅲ?Ⅳ,20(18.2%)had ECOG scores≥2,75(68.2%)had elevated lactate dehydrogenase(LDH)levels,79(71.8%)had≥2 extranodal involvements,32(31.4%)were classified as germinal center B-cell subtype,22(26.8%)were diagnosed with double expressor lymphoma,and 4(4.6%)with double-hit lymphoma.Among the patients treated with R-CHOP-based first-line regimens,the objective response rate(ORR)was 68.2%,the 5-year progression-free survival(PFS)rate was 43.7%,and the 5-year overall survival(OS)rate was 65.4%.Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS,and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations.Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS(HR=2.47,95%CI 1.28?4.77)and OS(HR=2.71,95%CI 1.21 ? 6.07).Targeted sequencing results showed that PIM1(25.7%),MYD88(24.3%),TP53(18.9%),CD79B(17.6%),KMT2D(17.6%),and TNFAIP3(16.2%)were the high-frequency mutations with mutation rates over 15%.Conclusion·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement.Mutations in PIM1,MYD88,TP53,CD79B,KMT2D,and TNFAIP3 are frequently observed in this population.

Homing pigeons and many other animals have exquisite geomagnetic sensing ability and can accurately find appropriate paths and directions during long-distance migration.Homing pigeons are the preferred animal model for studies of biological geomagnetic navigation.Despite substantial progress in research on bio-geomagnetic navigation over the past few decades,the biological mechanism is still unclear.In this paper,we review recent advancements in research on biological magnetoreception using homing pigeons.We focus on the magnetic sensing mechanisms of the magnetoreceptor models based on nanoscale ferromagnetic particles and the light-dependent radical pair model.Key directions for biological magnetoreception research are proposed.This review provides an improved theoretical basis for the study of geomagnetic navigation using homing pigeons as well as insight into the operating principles of the biological magnetic perception system.

This study investigated the prevalence of canine ticks and the types of their carried pathogens in select cities of Liaon-ing Province,to provide a theoretical scientific basis for the prevention and control of ticks and tick-borne diseases.Canine ticks were collected from six cities in Liaoning Province(Shenyang,Dalian,Anshan,Chaoyang,Tieling,Dandong)and identified through a combination of morphological and molecular biology methods.PCR was used to detect five tick pathogens:Rickettsia,Borrelia burgdor-feri,Babesia,Pseudomonas aeruginosa,and Ehrlichia.Canine ticks were prevalent primarily in Liaoning Province from April to June.The collected ticks included 456 Haemaphysalis longicornis,70 Ixodes persulcatus,and 31 Rhicephalus sanguineus.Three tick borne pathogens,Ehrlichia,Borrelia burgdorferi,and Rickettsia,were detected,whereas no Babesia or Pseudomonas were detected.The to-tal detection rate of Ehrlichia(46.85%),which is significant difference with total detection rate of Borrelia burgdorferi(10.81%)(χ2=33.392,P<0.05),but insignificant difference with total detection rate of Rickettsia(34.23%)(χ2=3.370,P>0.05),Both Eh-rlichia and Rickettsia were distributed in the six cities.Haemaphysalis longicornis was the dominant tick species parasite on the surfaces of dogs in Liaoning Province.The main tick borne pathogens in dogs in Liaoning Province were Ehrlichia and Rickettsia.