Periodontitis is a chronic inflammatory disease. The heterotopic colonization of periodontal pathogens results in the development of several systemic diseases. Porphyromonas gingivalis (P. gingivalis), a key pathogen for periodontitis, has been linked to the development of various cancers, such as oral squamous cell carcinoma (OSCC), lung cancer, esophageal cancer, pancreatic cancer, colorectal cancer, cervical cancer, and prostate cancer. P. gingivalis promote the progression of tumor through various mechanisms, P. gingivalis regulates proteins targeting cell cycle and apoptosis to promote proliferation of tumor cells directly, enhances tumor stemness by upregulating the expression of cluster of differentiation 44 (CD44) and cluster of differentiation 133 (CD133), activates inflammasome and p38/c-Jun N-terminal kinase 1(JNK) pathways, regulates tumor-associated neutrophil (TAN) polarization to remodel the tumor microenvironment, regulates epithelial-mesenchymal transition (EMT) to promote tumor metastasis, remodel macrophage function to evade host immune response, and regulates multi-communicating with symbiotic bacteria. In addition, P. gingivalis accelerates the progression of esophageal cancer, pancreatic cancer, colorectal cancer, and prostate cancer by promoting cell proliferation, inhibiting apoptosis, inducing chronic inflammation, and escaping immunity. However, the oral microbiome is a complex system, whether the interactions between oral bacteria affect tumor progression needs to be further investigated.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Objective: This study aims to understand the structure of meaning in life among patients with cancer through the validation of the Meaning in Life Scale among Korean patients (K-MiLS) with cancer. Methods: From August 2021 to November 2022, participants were recruited from multiple sites in South Korea. Participants completed related questionnaires, including the MiLS, on the web or mobile. Test-retest reliability was assessed between 2 and 4 weeks after the initial assessment. Exploratory and confirmatory factor analyses and Pearson’s correlations were used to evaluate the reliability and validity of the MiLS. A multiple regression analysis was conducted to examine the sociodemographic and disease-related variables correlated with the MiLS. Regarding concurrent validity, a hierarchical regression analysis was performed. Results: The results (n=345) indicated that the K-MiLS has a four-factor structure: Harmony and Peace; Life Perspective, Purpose, and Goals; Confusion and Lessened Meaning; and Benefits of Spirituality. Regarding convergent and discriminant validity, K-MiLS was negatively correlated with Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Fear of Cancer Recurrence Inventory while showing a significantly positive correlation with the Posttraumatic Growth Inventory, Self-Compassion Scale, Functional Assessment of Cancer Therapy-General, and Functional Social Support Questionnaire. Hierarchical regression analysis revealed that the demographic variable influencing MiLS was religious affiliation. Conclusion The K-MiLS had a multidimensional four-factor structure similar to that of the original version. It is also a reliable and valid measure for assessing cancer survivors’ meaning in life after a cancer diagnosis.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Objective: To investigate the safety and feasibility of transurethral blue laser vaporization of the prostate (BVP) under intravenous anesthesia without intubation. Methods: Clinical data of 30 benign prostatic hyperplasia (BPH) (prostate volume <40 mL) patients undergoing BVP under intravenous anesthesia without intubation in our hospital during Jul.and Nov.2024 were retrospectively analyzed.Preoperative and 1-month postoperative international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were compared.The operation time, cumulative blue laser activation time, recovery time, postoperative bladder irrigation time, postoperative catheter indwelling time, postoperative 2-hour visual analog scale (VAS) score and incidence of surgical and anesthetic complications were recorded. Results: All 30 patients successfully completed BVP under intravenous anesthesia without intubation.The operation time was (12.5±5.0) min, cumulative laser activation time (9.8±4.1) min, recovery time (6.8±1.2) min, postoperative bladder irrigation time (11.0±4.6) h, postoperative catheter indwelling time (2.7±1.1) days and postoperative 2-hour VAS score was (3.0±1.3).No cases required conversion to intubated general anesthesia, and no severe perioperative surgical or anesthetic complications occurred.Significant improvements in IPSS, QoL, Qmax, and PVR were observed 1 month postoperatively (P＜0.001). Conclusion: BVP under intravenous anesthesia without intubation in the treatment of prostate volume <40 mL BPH is clinically feasible, significantly improving lower urinary tract symptoms without significant surgical or anesthetic complications.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

The subcortical visual pathway is generally thought to be involved in dangerous information processing, such as fear processing and defensive behavior. A recent study, published in Human Brain Mapping, shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception. Rapid object processing is a critical function of visual system. Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property (TP). However, the mechanism of rapid TP processing remains unclear. The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation (TMS). They find that a subcortical magnocellular pathway is responsible for the early processing of TP, and this subcortical processing of TP accelerates object recognition. Based on their findings, we propose a novel training approach called subcortical magnocellular pathway training (SMPT), aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.