Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Objective:To explore the mechanism of how neurocognition affects social functioning through fa-cial emotion recognition in individuals with schizophrenia.Methods:Totally 203 patients with schizophrenia meet-ing the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-IV)diagnostic criteria were re-cruited,with an age of(40±12)years,an initial onset age of(24±8)years,scored(60.4±16.1)points on the Positive and Negative Syndrome Scale.Using the Personal and Social Performance Scale(PSP),the MATRICS Consensus Cognitive Battery(MCCB),and the Facial Emotion Recognition Test(FERT)to assess patients'social functioning,neurocognition,and facial emotion recognition abilities.Results:In the relationship between MCCB fac-tor scores and PSP dimensions scores,happy face recognition showed a mediating effect in socially useful activities dimension(ACME=0.021,P＜0.01),sad(ACME=-0.026,P＜0.05)and surprised face recognition(ACME=-0.017,P＜0.05)showed mediating effects in self-care dimension.Additionally,sad(ACME=-0.025,P＜0.05)and fearful face recognition(ACME=-0.025,P＜0.001)played a mediating role in disruptive and aggres-sive behavior dimensions.Conclusion:Facial emotion recognition in patients with schizophrenia may play a media-ting role in the neurocognitive mechanisms of social dysfunction,with different dimensions of social dysfunction be-ing associated with specific categories of emotions.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective:To study the relationship between human leukocyte antigen (HLA) Ⅱ and nuclear factor κB (NF-κB) gene polymorphisms and susceptibility to community-acquired pneumonia in children and the therapeutic effect of amoxicillin clavulanate potassium.Methods:A total of 120 children with community-acquired pneumonia admitted to the Baoding Second Central Hospital from February 2018 to January 2021 were selected as the study objects (observation group). According to the effect of amoxicillin and clavulanate potassium treatment, they were divided into effective group and ineffective group, and 120 healthy children in the same period were selected as the control group. The polymorphisms of HLAⅡ and NF-κB gene were compared between the two groups, and the correlation between the polymorphisms of HLAⅡ and NF-κB gene and the susceptibility of children to community-acquired pneumonia and the therapeutic effect of amoxicillin clavulanate potassium was analyzed.Results:The gene frequency of HLA-DQA1*0201 [86(71.67%) vs 40(33.33%)], HLA-DQA1*0301 [72(60.00%) vs 20(16.67%)] of the observation group was significantly higher than that of the control group, the gene frequency of HLA-DQA1*0401 [30(25.00%) vs 96(80.00%)] was significantly lower than that of control group (all P<0.05). The gene frequency of HLA-DRB1*07 [92(76.67%) vs 48(40.00%)], HLA-DRB1*15 [72(60.00%) vs 40(33.33%)], HLA-DRB1*16 [96(80.00%) vs 76(63.33%)] of the observation group was significantly higher than that of the control group, and the gene frequency of HLA-DRB1*11 [36(30.00%) vs 104(86.67%)] was significantly lower than that of control group (all P<0.05). The expression of 94ins/delATTG*II in the observation group was significantly higher than that in the control group [40(33.33%) vs 24(20.00%), P<0.05]. The gene frequency of HLA-DQA1*0201 [12(38.71%) vs 74(83.15%)], HLA-DQA1*0301 [9(29.03%) vs 63(70.79%)] in the ineffective group was significantly lower than that of the effective group, the gene frequency of HLA-DQA1*0401 [18(58.06%) vs 12(13.48%)] was significantly higher than that of the effective group (all P<0.05). The gene frequency of HLA-DRB1*07 [29(93.55%) vs 63(70.79%)], HLA-DRB1*15 [29(93.55%) vs 43(48.31%)], HLA-DRB1*16 [29(93.55%) vs 67(75.28%)] of the ineffective group was significantly higher than that of the effective group, and the gene frequency of HLA-DRB1*11 [17(54.84%) vs 19(21.35%)] was significantly higher than that of the effective group (all P<0.05). The expression of 94ins/delATTG*II gene in the ineffective group was significantly higher than that in the effective group [15(48.39%) vs 25(28.09%), P<0.05]. Conclusions:Polymorphisms of HLAⅡ and NF-κB genes are associated with susceptibility to community-acquired pneumonia and efficacy of amoxicillin and clavulanate potassium in children.

Objective To understand the current status of the job competency of full-time healthcare-associated in-fection(HAI)management professionals in all levels and types of medical institutions across China,and provide in-formation and basis for professional training,competency improvement,and career planning.Methods The strati-fied sampling method was adopted to select HAI management professionals from medical institutions in 31 provin-cial-level administrative regions across the country as the research subjects.The designed content of questionnaire involved four parts,including the surveyed personnel's basic information,daily job competency assessment,satis-faction level towards the job,as well as opinions and suggestions on the management of full-time HAI management professionals.The assessment on daily job competency was divided into 13 dimensions,ranging from very incompe-tent to very competent in 5 levels.The scores of HAI management professionals with different professional back-grounds were compared and analyzed.Results A total of 8 709 valid questionnaires were collected,with 3 475 and 3 697 surveyed personnel from tertiary and secondary medical institutions,respectively,and 1 537 from primary or unclassified medical institutions.The overall average score for the competency assessment of full-time HAI manage-ment professionals was(4.17±0.80)points.The scores of professionals with different professional backgrounds,from high to low,were as follows:nursing([4.12±0.81]points),clinical medicine([4.07±0.86]points),pre-ventive medicine([3.93±0.92]points),laboratory medicine([3.88±0.93]points),pharmacy([3.86±0.94]points),and health management([3.85±0.95]points).For the core competency of HAI management professio-nals,such as monitoring and analyzing HAI cases,identifying and investigating HAI outbreaks,the assessment scores for professionals with medical backgrounds were the highest(both P＜0.05).For the basic work of HAI prevention and control,such as checking and guiding the implementation of rules and regulations,guiding occupa-tional protection,management and communication,and implementing HAI management training,professionals with a nursing background had the highest assessment scores(all P＜0.05).Full-time HAI management professionals were relatively satisfied with their training,while those with a background in preventive medicine had lower satisfac-tion with their training,career development,and job benefits(all P＜0.05).Conclusion There are significant differences in the competency of HAI management professionals with different professional backgrounds.It is nece-ssary to optimize division of labor and leverage the strengths,providing ideas and models for promoting the construction of a specialized and professional HAI management team.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.

Objective:To study the relationship between human leukocyte antigen (HLA) Ⅱ and nuclear factor κB (NF-κB) gene polymorphisms and susceptibility to community-acquired pneumonia in children and the therapeutic effect of amoxicillin clavulanate potassium.Methods:A total of 120 children with community-acquired pneumonia admitted to the Baoding Second Central Hospital from February 2018 to January 2021 were selected as the study objects (observation group). According to the effect of amoxicillin and clavulanate potassium treatment, they were divided into effective group and ineffective group, and 120 healthy children in the same period were selected as the control group. The polymorphisms of HLAⅡ and NF-κB gene were compared between the two groups, and the correlation between the polymorphisms of HLAⅡ and NF-κB gene and the susceptibility of children to community-acquired pneumonia and the therapeutic effect of amoxicillin clavulanate potassium was analyzed.Results:The gene frequency of HLA-DQA1*0201 [86(71.67%) vs 40(33.33%)], HLA-DQA1*0301 [72(60.00%) vs 20(16.67%)] of the observation group was significantly higher than that of the control group, the gene frequency of HLA-DQA1*0401 [30(25.00%) vs 96(80.00%)] was significantly lower than that of control group (all P<0.05). The gene frequency of HLA-DRB1*07 [92(76.67%) vs 48(40.00%)], HLA-DRB1*15 [72(60.00%) vs 40(33.33%)], HLA-DRB1*16 [96(80.00%) vs 76(63.33%)] of the observation group was significantly higher than that of the control group, and the gene frequency of HLA-DRB1*11 [36(30.00%) vs 104(86.67%)] was significantly lower than that of control group (all P<0.05). The expression of 94ins/delATTG*II in the observation group was significantly higher than that in the control group [40(33.33%) vs 24(20.00%), P<0.05]. The gene frequency of HLA-DQA1*0201 [12(38.71%) vs 74(83.15%)], HLA-DQA1*0301 [9(29.03%) vs 63(70.79%)] in the ineffective group was significantly lower than that of the effective group, the gene frequency of HLA-DQA1*0401 [18(58.06%) vs 12(13.48%)] was significantly higher than that of the effective group (all P<0.05). The gene frequency of HLA-DRB1*07 [29(93.55%) vs 63(70.79%)], HLA-DRB1*15 [29(93.55%) vs 43(48.31%)], HLA-DRB1*16 [29(93.55%) vs 67(75.28%)] of the ineffective group was significantly higher than that of the effective group, and the gene frequency of HLA-DRB1*11 [17(54.84%) vs 19(21.35%)] was significantly higher than that of the effective group (all P<0.05). The expression of 94ins/delATTG*II gene in the ineffective group was significantly higher than that in the effective group [15(48.39%) vs 25(28.09%), P<0.05]. Conclusions:Polymorphisms of HLAⅡ and NF-κB genes are associated with susceptibility to community-acquired pneumonia and efficacy of amoxicillin and clavulanate potassium in children.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis