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.

ObjectiveTo investigate the effect of Semaphorin 3A （Sema3A） on the progression of pathological cardiac hypertrophy. MethodsWild-type C57BL 6J mice， Sema3A global overexpressing （Sema3A/Cre-ER^TM） mice， and their littermate controls （Cre-ER^TM） were used， with 6 mice per group. A pressure-overload induced cardiac hypertrophy model was established via transverse aortic constriction （TAC）， with a sham-operated group （Sham） as the control. Cardiac hypertrophy was assessed by gross morphology， heart weight/body weight ratio （HW/BW）， heart weight/tibia length ratio （HW/HL）， and heart weight/lung weight ratio （HW/PW）. Cardiac function was evaluated by measuring ejection fraction （EF） and fractional shortening （FS） via echocardiography. In heart tissues， the mRNA level of atrial natriuretic peptide （ANP） and Sema3A were detected by RT-qPCR， Sema3A protein level was detected by western blot， morphological structure was detected by hematoxylin and eosin （HE） staining， level of fibrosis was detected by Masson’s trichrome staining， and angiogenesis was detected by immunohistochemical detection of CD31. For in vitro experiments， rat H9C2 cardiomyocytes were treated with angiotensin Ⅱ （Ang Ⅱ） to induce hypertrophy， with PBS-treated cells as the control. After 48 hours， the mRNA expression of ANP， B-type natriuretic peptide （BNP） and Sema3A were measured by RT-qPCR， and Sema3A protein level was assessed by western blot. ResultsAt the animal level， compared with the sham group， mice subjected to TAC showed significantly increased mRNA levels of ANP in cardiac tissue， as well as markedly elevated mRNA and protein levels of Sema3A （all P<0.05）. Compared with the Cre-ER^TM + TAC group， the Sema3A/Cre-ER^TM + TAC group exhibited more pronounced cardiac hypertrophy， greater ventricular wall thickening， higher HW/BW， HW/HL， and HW/PW ratios， more significant reductions in EF and FS， more severe cardiac fibrosis， and a significant decrease in cardiac CD31 expression levels （all P<0.05）. At the cellular level， compared with the control group， H9C2 cells treated with Ang Ⅱ displayed significantly increased mRNA levels of ANP and BNP， along with markedly elevated mRNA and protein levels of Sema3A （all P<0.05）. ConclusionSema3A promotes the progression of pressure overload-induced cardiac hypertrophy by inhibiting angiogenesis.

ObjectiveTo investigate the mechanism by which Kangxian Yixin prescription regulates the circular RNA 0006719 （circ0006719）/microRNA 6852-5p （miR-6852-5p）/transforming growth factor-β₁ （TGF-β₁）/Smad axis to ameliorate myocardial fibrosis in rats with dilated cardiomyopathy （DCM） and angiotensin Ⅱ （Ang Ⅱ）-induced activation of cardiac fibroblasts （CFs）. MethodsA DCM rat model was established by administration of furazolidone. The rats were divided into normal group， model group， captopril （CAP， 10.1 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose Kangxian Yixin prescription groups （0.9， 1.8， 3.6 g·kg^-1·d^-1）， with 15 rats in each group. After modeling， the treatment groups received corresponding drug solutions by gavage， whereas the normal and model groups received an equal volume of normal saline for 60 consecutive days. Echocardiography was used to measure left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular ejection fraction （LVEF）， and left ventricular fractional shortening （LVFS）. Transmission electron microscopy （TEM）， hematoxylin-eosin （HE） staining， and Masson staining were used to observe myocardial ultrastructure， pathological changes， and collagen deposition. Immunohistochemistry （IHC） was used to detect the protein expression of collagen type Ⅰ alpha 1 （Col1A1） and collagen type Ⅲ（Col Ⅲ） in myocardial tissue. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and fluorescence in situ hybridization （FISH） were used to detect the expression and localization of circ0006719， miR-6852-5p， fibrosis-related molecules， and TGF-β₁/Smad pathway-related molecules in myocardial tissue and CFs. CFs from neonatal rats were isolated and cultured in vitro. Cell Counting Kit-8 （CCK-8） assay was used to determine the optimal concentration of Kangxian Yixin prescription for subsequent intervention. An Ang Ⅱ-induced CF activation model was established， and the cells were divided into normal group， Ang Ⅱ group， Ang Ⅱ+CAP group， Ang Ⅱ+Kangxian Yixin prescription group， and Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group. CF viability and fibrosis-related molecular expression were detected. RNA immunoprecipitation （RNA IP） and dual-luciferase reporter assays were used to verify the targeting relationship between circ0006719 and miR-6852-5p. ResultsCompared with the normal group， the model group showed significantly increased LVESD and LVEDD， significantly decreased LVEF and LVFS， aggravated myocardial ultrastructural and histopathological injury， and significantly increased collagen volume fraction （CVF） in myocardial tissue （P<0.01）. The expression of circ0006719， Col1A1 mRNA， Col ⅢmRNA， and Col1A1， Col Ⅲ， TGF-β₁， Smad3， and Smad4 proteins in myocardial tissue was significantly upregulated， whereas miR-6852-5p expression and Smad7 protein expression were significantly downregulated （P<0.01）. Compared with the model group， the CAP group and the high- and medium-dose Kangxian Yixin prescription groups showed varying degrees of improvement in cardiac function， myocardial fibrosis， circ0006719/miR-6852-5p expression， and TGF-β₁/Smad pathway-related indicators， with more pronounced improvements in the CAP group and the high-dose Kangxian Yixin prescription group （P<0.05， P<0.01）. In in vitro experiments， 2.0 g·L^-1 was determined as the optimal concentration of Kangxian Yixin prescription for subsequent intervention. Compared with the normal group， the Ang Ⅱ group showed significantly increased CF viability， significantly upregulated expression of circ0006719， Col1A1 mRNA， α-smooth muscle actin （α-SMA） mRNA， and Col1A1， α-SMA， TGF-β₁， Smad3， and Smad4 proteins in CFs， and significantly downregulated miR-6852-5p expression and Smad7 protein expression （P<0.01）. Compared with the Ang Ⅱ group， the Ang Ⅱ+CAP group and the Ang Ⅱ+Kangxian Yixin prescription group showed markedly decreased CF viability and fibrosis-related mRNA and protein expression， markedly increased miR-6852-5p expression， and markedly attenuated TGF-β₁/Smad pathway activation （P<0.05， P<0.01）. Compared with the Ang Ⅱ+Kangxian Yixin prescription group， the Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group showed significantly increased CF viability （P<0.01）， markedly increased expression of circ0006719， Col1A1 mRNA， and Col1A1， TGF-β₁， and Smad4 proteins in CFs， and markedly decreased miR-6852-5p expression （P<0.05， P<0.01）. RNA IP and dual-luciferase reporter assays showed a targeting binding relationship between circ0006719 and miR-6852-5p （P<0.01）. ConclusionKangxian Yixin prescription may alleviate myocardial collagen deposition and myocardial fibrosis， improve cardiac function in DCM rats， and inhibit Ang Ⅱ-induced abnormal activation of CFs. Its mechanism may be associated with downregulation of circ0006719， restoration of miR-6852-5p expression， and inhibition of the TGF-β₁/Smad pathway.

ObjectiveTo investigate the mechanism by which Kangxian Yixin prescription regulates the circular RNA 0006719 （circ0006719）/microRNA 6852-5p （miR-6852-5p）/transforming growth factor-β₁ （TGF-β₁）/Smad axis to ameliorate myocardial fibrosis in rats with dilated cardiomyopathy （DCM） and angiotensin Ⅱ （Ang Ⅱ）-induced activation of cardiac fibroblasts （CFs）. MethodsA DCM rat model was established by administration of furazolidone. The rats were divided into normal group， model group， captopril （CAP， 10.1 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose Kangxian Yixin prescription groups （0.9， 1.8， 3.6 g·kg^-1·d^-1）， with 15 rats in each group. After modeling， the treatment groups received corresponding drug solutions by gavage， whereas the normal and model groups received an equal volume of normal saline for 60 consecutive days. Echocardiography was used to measure left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular ejection fraction （LVEF）， and left ventricular fractional shortening （LVFS）. Transmission electron microscopy （TEM）， hematoxylin-eosin （HE） staining， and Masson staining were used to observe myocardial ultrastructure， pathological changes， and collagen deposition. Immunohistochemistry （IHC） was used to detect the protein expression of collagen type Ⅰ alpha 1 （Col1A1） and collagen type Ⅲ（Col Ⅲ） in myocardial tissue. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and fluorescence in situ hybridization （FISH） were used to detect the expression and localization of circ0006719， miR-6852-5p， fibrosis-related molecules， and TGF-β₁/Smad pathway-related molecules in myocardial tissue and CFs. CFs from neonatal rats were isolated and cultured in vitro. Cell Counting Kit-8 （CCK-8） assay was used to determine the optimal concentration of Kangxian Yixin prescription for subsequent intervention. An Ang Ⅱ-induced CF activation model was established， and the cells were divided into normal group， Ang Ⅱ group， Ang Ⅱ+CAP group， Ang Ⅱ+Kangxian Yixin prescription group， and Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group. CF viability and fibrosis-related molecular expression were detected. RNA immunoprecipitation （RNA IP） and dual-luciferase reporter assays were used to verify the targeting relationship between circ0006719 and miR-6852-5p. ResultsCompared with the normal group， the model group showed significantly increased LVESD and LVEDD， significantly decreased LVEF and LVFS， aggravated myocardial ultrastructural and histopathological injury， and significantly increased collagen volume fraction （CVF） in myocardial tissue （P<0.01）. The expression of circ0006719， Col1A1 mRNA， Col ⅢmRNA， and Col1A1， Col Ⅲ， TGF-β₁， Smad3， and Smad4 proteins in myocardial tissue was significantly upregulated， whereas miR-6852-5p expression and Smad7 protein expression were significantly downregulated （P<0.01）. Compared with the model group， the CAP group and the high- and medium-dose Kangxian Yixin prescription groups showed varying degrees of improvement in cardiac function， myocardial fibrosis， circ0006719/miR-6852-5p expression， and TGF-β₁/Smad pathway-related indicators， with more pronounced improvements in the CAP group and the high-dose Kangxian Yixin prescription group （P<0.05， P<0.01）. In in vitro experiments， 2.0 g·L^-1 was determined as the optimal concentration of Kangxian Yixin prescription for subsequent intervention. Compared with the normal group， the Ang Ⅱ group showed significantly increased CF viability， significantly upregulated expression of circ0006719， Col1A1 mRNA， α-smooth muscle actin （α-SMA） mRNA， and Col1A1， α-SMA， TGF-β₁， Smad3， and Smad4 proteins in CFs， and significantly downregulated miR-6852-5p expression and Smad7 protein expression （P<0.01）. Compared with the Ang Ⅱ group， the Ang Ⅱ+CAP group and the Ang Ⅱ+Kangxian Yixin prescription group showed markedly decreased CF viability and fibrosis-related mRNA and protein expression， markedly increased miR-6852-5p expression， and markedly attenuated TGF-β₁/Smad pathway activation （P<0.05， P<0.01）. Compared with the Ang Ⅱ+Kangxian Yixin prescription group， the Ang Ⅱ+Kangxian Yixin prescription+miR-6852-5p inhibitor group showed significantly increased CF viability （P<0.01）， markedly increased expression of circ0006719， Col1A1 mRNA， and Col1A1， TGF-β₁， and Smad4 proteins in CFs， and markedly decreased miR-6852-5p expression （P<0.05， P<0.01）. RNA IP and dual-luciferase reporter assays showed a targeting binding relationship between circ0006719 and miR-6852-5p （P<0.01）. ConclusionKangxian Yixin prescription may alleviate myocardial collagen deposition and myocardial fibrosis， improve cardiac function in DCM rats， and inhibit Ang Ⅱ-induced abnormal activation of CFs. Its mechanism may be associated with downregulation of circ0006719， restoration of miR-6852-5p expression， and inhibition of the TGF-β₁/Smad pathway.

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

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent