ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Objective To explore the risk factors for postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB) alone. Methods A retrospective analysis was conducted on the clinical data of patients who underwent OPCAB in the Department of Cardiac Surgery Ward No.1 of Zhengzhou Seventh People’s Hospital from January 2020 to January 2024. Patients were categorized into a POAF group and a non-POAF group based on the occurrence of POAF. The clinical data of both groups were analyzed. Parameters underwent univariate analysis, and variables with P≤0.05 in univariate analysis were further analyzed through binary multivariate logistic regression to identify independent risk factors. Results A total of 496 patients were included. There were 312 males and 184 females, with age ranging from 50 to 78 years. There were 148 patients in the POAF group and 348 patients in the non-POAF group. The incidence of POAF after isolated OPCAB surgery was 29.8%. Results of univariate analysis showed that there were statistical differences in the incidence of diabetes (P=0.012), >75% stenosis of the left circumflex artery (LCX) (P=0.036), shock (P<0.001), graded left ventricular diastolic function (P<0.001), left ventricular ejection fraction (P<0.001), age (P<0.001), preoperative resting heart rate (P<0.001), left atrial diameter (P<0.001), E/A ratio (P<0.001), postoperative K+ concentration (P<0.001), and postoperative Mg2+ concentration (P<0.001). Binary multivariate logistic regression analysis revealed that age (OR=1.436, 95%CI 1.094 to 1.884, P=0.009), diabetes (OR=2.032, 95%CI 1.006 to 4.145, P=0.043), preoperative resting heart rate (OR=1.008, 95%CI 1.001 to 1.015, P=0.018), left atrial diameter (OR=4.409, 95%CI 1.711 to 11.359, P=0.002), and E/A ratio (OR=1.713, 95%CI 1.115 to 2.633, P=0.014) were independent risk factors for POAF after isolated OPCAB. The occurrence of POAF significantly prolonged mechanical ventilation time and ICU stay (both P＜0.001). Conclusion Age, diabetes, left atrial diameter, E/A ratio, and preoperative resting heart rate are potential independent risk factors for POAF following OPCAB surgery. Additionally, the occurrence of POAF can lead to prolonged mechanical ventilation and extended stay in the intensive care unit.

Alzheimer's disease （AD） is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein （Aβ） excessive deposition， neuroinflammatory response， Tau protein hyperphosphorylation， and other factors， and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single， so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow， as well as the loss of vital energy， is the internal mechanisms underlying the occurrence and development of AD， which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）. Activating the NLRP3 signaling pathway increases neuroinflammatory response， intervenes in microglial polarization， and regulates Aβ sedimentation， cellular autophagy， brain homeostasis， etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years， as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds， such as Danggui Shaoyaosan， modified Shuyu Wan， Qingxin Kaiqiao prescription， Kaixin San， Jiedu Yizhi prescription， and modified Buwang San， traditional Chinese medicine monomer extracts， such as silibinin， Lycium barbarum polysaccharides， liquiritigenin， salidroside， baicalin， cinnamaldehyde， betaine， acacetin， and Hericium erinaceus， and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

ObjectiveTo investigate the effect of Fuhe Decoction （敷和汤） with different doses of Suanzaoren （Ziziphus jujuba） for atopic dermatitis （AD）. MethodsForty-eight female BALB/c mice were randomly divided into normal group， model group， loratadine group， and Fuhe Decoction groups with high， medium， and low doses of Fuhe Decoction （Fuhe Decoction high-， medium-， and low-dose groups）， with eight mice in each group. The AD model was prepared by continuous stimulation with 2，4-dinitrofluorobenzene （DNFB） in all groups but the normal group. After modelling， the Fuhe Decoction high-， medium- and low-dose groups were given 24， 18 and 15 g/（kg·d） of Fuhe Decoction， the loratadine group was given 0.001 g/（kg·d） of loratadine dry suspension， and the normal group and the model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 14 days. The number of scratches within 10 min and the score of skin lesions were observed on the 7th and 14th days of modelling and on the 7th and 14th days of drug administration， respectively； serum immunoglobulin E （IgE） was detected by ELISA； the histopathological and morphological changes of the skin were observed by HE staining； and the diversity and abundance of intestinal flora were detected by 16S rRNA sequencing of fecal matter from the colon of the mice. ResultsCompared with the normal group， mice in the model group on the 7th day and the 14th day of modelling and the 7th day， the 14th day of gavage showed increased scratching within 10 min and higher skin lesion scores （P＜0.05）， with hyperkeratotic or incomplete epidermis， marked thickening of spiny cells， and a large number of inflammatory cells infiltrated in the mice after gavage； serum levels of IgE elevated （P＜0.05）， and the abundance of Bacillota decreased， that of the Bacteroidota and bacteria elevated， and relative abundance of Lactobacillus spp. and Prevotella spp. decreased， and relative abundance of Anaplasma spp. and Treponema spp. increased （P＜0.05）. Compared with the model group， the number of scratches within 10 min and the skin lesion scores of mice in the loratadine group and the Fuhe Decoction medium- and high-dose groups decreased on the 7th day and the 14th day of gavage （P＜0.05）， serum IgE reduced， and the bacteria reduced in the loratadine group， the abundance of Bacteroidesmus spp. increased and Bacteriodesmus spp. decreased in the medium-dose group of Fuhe Decoction， the abundance of Bacteriodesmus spp. decreased in the loratadine group， the abundance of Bacteriodesmus spp. decreased， and that of both Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction medium-dose group （P＜0.05）. Compared with the loratadine group， the skin lesion scores increased in Fuhe Decoction low-dose group， and the number of scratching increased in the Fuhe Decoction low- and high-dose groups on the 7th day and the 14th day of gavage； the IgE content increased in Fuhe Decoction low-dose group， the Bacillota increased and the Bacteroidota decreased， the Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction middle-dose group， and Anopheles spp. increased in Fuhe Decoction high-dose group after gavage （P＜0.05）. ConclusionFuhe Decoction can improve the clinical symptoms of AD， regulate the relative abundance of intestinal flora to correct the disorders of the bacterial flora， among which the effect of Fuhe Decoction medium-dose group is optimal and comparable to that of the loratadine group， and the reduction of serum IgE inflammatory response may be one of its mechanisms of action.

Objective To explore the effect of histologic chorioamnionitis(HCA)on clinical outcomes of preterm infants with a gestational age<34 weeks.Methods This retrospective study enrolled 497 cases of premature infants with a gestational age<34 weeks and their mothers who were hospitalized in the Qingdao Women and Children's Hospital from January 2019 to December 2022.According to whether the pathology of placenta was diagnosed as HCA or not,patients were divided into the HCA group(257 cases)and the control group(240 cases).The propensity score matching analysis was performed at a ratio of 1︰1.Ten items were matched,including gestational age,birth weight,gender,cesarean section,gestational diabetes mellitus,gestational hypertension,placental abruption,premature rupture of membranes,use of antenatal glucocorticoids and assisted reproductive technology.The differences of major complications and survival rate were compared between the two groups.Results A total of 156 pairs premature infants were successfully matched.Before matching,the incidences of early-onset sepsis(EOS)and bronchopulmonary dysplasia(BPD)were higher in the HCA group than those of the control group(26.1%vs.7.5%,45.1%vs.25.8%,P＜0.01).The incidence of EOS was higher in the HCA group than that of the control group after matching(24.4%vs.7.7%,P＜0.01),and the incidence of neonatal respiratory distress syndrome(NRDS)was significantly lower in the HCA group than that in the control group after matching(34.0%vs.46.8%,P＜0.05).There were no significant differences in survival rate and the incidences of other complications between the two groups before and after matching(P>0.05).Conclusion Preterm infants exposed to HCA have a higher risk of EOS and a lower risk of NRDS after propensity score matching.HCA has no significant effect on survival rate and other complications of premature infants.