Objective To implement the disease prevention and control strategy of being ^"proactive and grassroots-focused,^" and to enhance the overall effectiveness of general hospitals in the tertiary prevention of cervical cancer, this consensus aims to provide an actionable guiding framework for the standardized construction of ^"Integrated Outpatient Clinics for Cervical Cancer Prevention and Control^" in general hospitals at all levels. Methods This consensus systematically elaborates on the specific elements for establishing such integrated clinics and formulates the corresponding standards. Results It is anticipated that the consensus will promote the establishment of standardized, homogeneous, and high-efficiency frontline positions for cervical cancer prevention and control within general hospitals, thereby contributing to the strategic vision of accelerating the elimination of cervical cancer. Conclusion The formulation and promotion of the consensus aim to provide robust clinical practice support for accelerating the realization of China's strategic vision of eliminating cervical cancer.

Objective: To assess the causal association between specific oral microbiota and the risk of oral leukoplakia (OLK) using a Mendelian randomization (MR) approach, and to elucidate the potential mediating role of immune cells. Methods: Summary statistics from genome-wide association studies (GWAS) of the oral microbiome, GWAS data for immune cell phenotypes, and GWAS summary statistics for OLK from FinnGen were used. The inverse variance weighted (IVW) method was adopted as the primary approach, and it was supplemented by MR Egger regression, simple mode, weighted median, and weighted mode methods for additional analyses, to investigate the causal relationship between 3 117 types of tongue coating and salivary microbiota, as well as 731 immune cell traits, and OLK. Furthermore, a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK. Results: IVW analysis revealed causal associations between 15 oral microbial genera and OLK. Among these, Streptococcus, Neisseria, and Catonella were associated with a reduced risk of OLK, with Fusobacterium showing the most significant protective effect (OR = 0.41, P = 0.023). In contrast, genera, including Microbacterium, Campylobacter, and Haemophilus_A, were linked to an increased risk of OLK, with Lancefieldella exhibiting the strongest risk effect (OR = 2.66, P = 0.006). Eleven immune cell phenotypes with potential causal associations with OLK were identified, including four protective and seven risk-increasing factors. Mediation analysis further identified four key mediating pathways: pathogenic genera, particularly Campylobacter_A and Lancefieldella, may promote the development and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes, B cells, and myeloid cells. Conversely, the potentially protective genus Catonella appeared to exert inhibitory effects on OLK by significantly downregulating dendritic cell subsets. Conclusion This study is the first to reveal, at the genetic level, causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses. These findings provide novel insights into the immunopathological mechanisms underlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or immune cell subsets.

Objective: To explore the effects of microwave radiation on cognitive function and neuroinflammation in mice with experimental periodontitis, providing experimental evidence for understanding how environmental exposure may be linked to the risk of neurodegenerative diseases by modulating chronic inflammation as a shared pathological mechanism Methods: This study was approved by the Animal Ethics Committee of the Academy of Military Medical Sciences. C57BL/6J mice were randomly divided into a control group (C group, untreated), a microwave radiation group (R group, exposed to microwave radiation only), a periodontitis group (P group, ligation-induced periodontitis only), and a periodontitis + microwave radiation group (PR group, ligation-induced periodontitis plus microwave radiation exposure). A periodontitis model was established using the silk ligation method. Eight weeks after modeling, the R and PR groups were subjected to whole-body microwave radiation at 2 800 MHz and 10 mW/cm2 for 10 h/day for 7 consecutive days. Behavioral tests were conducted: the open field test and elevated plus maze test were used to assess anxiety-like behavior, the Y-maze test to evaluate spatial memory, and the novel object recognition test to assess learning and memory abilities. Micro-CT, hematoxylin & eosin staining (HE), and quantitative real-time polymerase chain reaction (qPCR) were used to analyze periodontal tissue pathology and local inflammation. Serum and brain levels of lipopolysaccharide (LPS), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). The composition of the oral microbiota was analyzed based on 16S rRNA sequencing. Results: Behavioral tests showed that anxiety-like behavior was significantly exacerbated in the R and PR groups, and spatial and recognition memory impairments in the PR and P groups were more severe compared with the R and C groups, respectively (P < 0.05). Histological and molecular biological analyses revealed that periodontal inflammation infiltration, alveolar bone resorption, and local expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) were further exacerbated in the PR and P groups compared with the R and C groups, respectively (P < 0.05). ELISA results showed that in serum, LPS levels in group P and group PR were increased compared with group C and group R, respectively. The levels of TNF-α, IL-1β, and IL-6 in group PR were significantly higher than those in group P and group R, with a synergistic increase in TNF-α level (P < 0.05). In brain tissue, LPS and TNF-α, IL-1β, IL-6 levels in group P were significantly higher than those in group C; all the above indicators in group PR were significantly higher than those in group P and group R, and LPS and IL-6 levels showed a synergistic increase (P < 0.05). Oral microbiota analysis found that microwave radiation further reduced microbial diversity on the basis of periodontitis, leading to increased relative abundances of Lactobacillus and Enterococcus, and decreased relative abundances of Staphylococcus. Correlation analysis confirmed that these differential bacterial genera were positively correlated with brain inflammation levels and negatively correlated with cognitive function indicators. Conclusion Microwave radiation exposure can exacerbate cognitive impairment in mice with experimental periodontitis, and its mechanism may be related to aggravated local periodontal damage, disruption of oral microbiota homeostasis, and subsequent induction of systemic and central neuroinflammatory cascades.

Locoregional therapy （LRT）， including transarterial chemoembolization， transarterial radioembolization， and various ablation techniques， is an important treatment method for hepatocellular carcinoma. Many studies in recent years have confirmed that LRT has a dual regulatory effect on tumor immune microenvironment. While LRT induces immunogenic cell death， activates dendritic cell-mediated and T cell-driven immunity， and triggers systemic antitumor responses， it concomitantly upregulates the adenosine signaling pathway， promotes the accumulation of TREM2⁺ macrophages， and enhances the expression of immunosuppressive factors， thereby forming an immunosuppressive microenvironment. At present， the combination of LRT and immune checkpoint inhibitors has shown a promising future and has promoted the exploration of novel targets within treatment-associated immunosuppressive pathways， such as adenosine， TREM2⁺ macrophages， and IL-6. This article summarizes the dual regulatory effect of LRT on immune microenvironment and highlights that multi-omics techniques and clinical trials should be used in the future to decipher its dynamic alterations， in order to optimize combination strategies， realize individualized precise treatment， and improve the prognosis of patients.

Objective:To investigate the clinical characteristics and risk factors associated with secondary systemic capillary leak syndrome (SSCLS) induced by acute organophosphorus pesticide poisoning (AOPP). The goal is to enhance clinical understanding of this complication and provide a theoretical foundation for the early identification of high-risk patients and the optimization of individualized treatment strategies.Methods:Clinical data were collected from patients admitted to the Emergency Department of Fuyang People’s Hospital Affiliated to Anhui Medical University between October 2019 and October 2024, who were diagnosed with acute dichlorvos poisoning. The clinical features of SSCLS were described, and patients were categorized into SSCLS and non-SSCLS groups. Binary multivariate logistic regression analysis was conducted on statistically significant indicators to identify independent risk factors for SSCLS. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of these factors.Results:Among the 96 patients studied, 37 (38.5%) developed SSCLS. The median time from toxin ingestion to the onset of SSCLS was 3.0 (2.0-5.0) hours. In the 14 SSCLS survivors, the median duration of SSCLS was 50.0 (24-72) hours, whereas in the 23 non-survivors, it was 24.0 (12.0-35.0) hours. The mortality rate in the SSCLS group (62.16%, 23/37) was significantly higher than that in the non-SSCLS group (1.69%, 1/59) ( χ2=44.343, P<0.001). Blood toxin analysis detected trichlorfon components in 92 patients (95.83%). Binary multivariate logistic regression identified APACHE Ⅱ score and trichlorfon concentration (≥706.35 ng/mL) as independent risk factors for SSCLS ( P<0.05). ROC analysis revealed that the combination of these two factors had a higher predictive value ( P<0.05). Conclusions:In the diagnosis and treatment of acute dichlorvos (organophosphorus pesticide) poisoning, particular attention should be given to the combined toxic effects of dichlorvos and trichlorfon, which can lead to SSCLS. The onset and progression of SSCLS are rapid, and the condition is associated with a high mortality rate. Both APACHE Ⅱ scores and trichlorfon concentrations (≥706.35 ng/mL) are independent risk factors for the development of SSCLS, and their combined use enhances predictive accuracy. Early identification of high-risk patients and timely administration of individualized treatment are critical for reducing mortality rates. This revised abstract maintains the original meaning while improving clarity, flow, and readability. It ensures that the key points are presented in a structured and professional manner, suitable for a clinical audience.

As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Q_m) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

Objective To construct a Nomogram prediction model for short-term prognosis of coronary heart disease(CAD)patients with hypertension after percutaneous coronary intervention(PCI)based on re-nin-angiotensin-aldosterone(ALD)system(RAAS)and Syntax score of coronary artery disease,so as to pro-vide a favorable basis for improving the prognosis of patients.Methods A total of 310 CAD patients with hy-pertension admitted to Jintang Hospital of West China Hospital of Sichuan University from June 2019 to April 2023 were selected.According to the ratio of 7:3,310 patients were randomly divided into a training set(217 cases)and a validation set(93 cases).All patients underwent PCI and were followed up for 3 months.The training set was further divided into poor prognosis group(n=68)and good prognosis group(n=148)ac-cording to the incidence of major adverse cardiovascular events(MACE).Multivariate Logistic regression model was used to analyze the risk factors of poor prognosis.The Nomogram prediction model was construc-ted by the R language in the training set,and the calibration curve and receiver operating characteristic(ROC)curve were used to verify the prediction efficiency of the model in the validation set.Results There was no significant difference in the general data between the training set and the validation set(P>0.05).MACE oc-curred in 68 cases(31.34％)in the training set and 28 cases(30.11％)in the validation set.There were sig-nificant differences in age,left ventricular ejection fraction,creatine kinase isoenzyme(CK-MB),number of diseased vessels,renin activity(PRA),angiotensin Ⅱ(ANG Ⅱ),ALD,preoperative Syntax score and N-termi-nal pro-B-type brain natriuretic peptide(NT-proBNP)between the good prognosis group and the poor prog-nosis group(P<0.05).Pearson correlation analysis showed that PRA,ANGⅡ,ALD were positively correla-ted with preoperative Syntax score(r=0.613,0.728,0.695,P<0.05).Lasso regression analysis included age,left ventricular ejection fraction,number of diseased vessels,PRA,ANG Ⅱ,ALD,preoperative Syntax score.Multivariate Logistic regression analysis showed that age,left ventricular ejection fraction,number of diseased vessels,PRA,ANG Ⅱ,ALD and preoperative Syntax score were independent influencing factors for poor short-term prognosis of PCI treatment(OR=4.448,5.153,4.571,3.875,4.914,4.468,5.224,P<0.05).The ROC curve showed that the area under the curve(AUC)of the Nomogram prediction model for poor short-term prognosis of CAD patients with hypertension after PCI in the training set and validation set were 0.884(95％CI 0.837-0.931)and 0.885(95％CI 0.818-0.953),respectively.The calibration curve showed that the prediction probability of poor short-term outcome of PCI in the training set and the validation set was basically consistent with the actual probability.Conclusion The short-term prognosis of CAD patients with hypertension after PCI is affected by age,left ventricular ejection fraction,number of diseased vessels,PRA,ANG Ⅱ,ALD,preoperative Syntax score and other factors.The Nomogram prediction model based on the above factors has high predictive value and good predictive utility.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female