ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

Objective Mendelian randomization was used to analyze the causal association between 20 serum metabolites and the risk of ovarian cancer.Methods The gene variations of 20 serum metabolites were obtained from the MRC IEU database as tool variables reflecting exposure levels,while gene variations of ovarian cancer patients were used as instrumental variables reflecting outcome levels.The ovarian cancer dataset ieu-a-1120 included 66,450 European women samples(of which 25,509 were ovarian cancer),and the dataset ieu-a-1228 included 54,990 European women samples(of which 14,049 were ovarian cancer).Two-sample two-way Mendelian randomization analysis was performed on both datasets.This study used inverse variance-weighted(IVW),weigh-ted median method,MR-Egger regression,and combined various analysis methods such as simple mode,and weighted mode.The caus-al effects of 20 metabolites and the risk of ovarian cancer were analyzed.Cochran's Q test was used to perform sensitivity analysis and to verify the reliability of the results.MR Egger intercept test was used to assess the horizontal pleiotropy of tool variables,and use the leave-one-out method to assess whether there were single nucleotide polymorphisms(SNPs)in the results that might have a potential impact on the incidence of ovarian cancer.Finally,the effects of uridine on ovarian cancer cells were verified through cell proliferation and apoptosis experiments.Results The results showed a negative correlation between uridine and the occurrence of ovarian cancer,with statistically significance(ieu-a-1228:P=0.025;ieu-a-1120:P=0.017).MR-Egger regression analysis confirmed the sensitiv-ity and robustness of the analysis results.The CCK8 assay confirmed that uridine inhibited the proliferation of ovarian cancer cells in a concentration-dependent manner,and uridine at a concentration of 10 mM significantly promoted apoptosis in SKOV3 cells(P<0.001)and A2780 cells(P<0.001).Flow cytometry analysis showed that after treatment for 24 hours,uridine at a concentration of 10 mM had the strongest pro-apoptotic effect on ovarian cancer cells,which was significant in SKOV3 and A2780 cells(P<0.05 and P<0.001,respectively).Conclusion Uridine is negatively correlated with the risk of ovarian cancer,which lays a theoretical founda-tion for further understanding the pathogenesis of ovarian cancer and optimizing clinical treatment strategies.

Objective To evaluate the effect of five-element music combined with sandplay therapy in improving negative emotions and enhancing quality of life in patients with malignant tumors.Methods A to-tal of 112 malignant tumor patients meeting inclusion and exclusion criterias were enrolled and randomly di-vided into four groups by using random number table method:control group,five-element music group,sand-play therapy group,and combined therapy group,with 28 patients in every group.The control group received routine nursing and psychological care;the five-element music group received routine nursing,psychological care and five-element music therapy;the sandplay therapy group received routine nursing,psychological care,and sandplay therapy;the combined therapy group received routine nursing,psychological care,five-element music,and sandplay therapy.Interventions were conducted once a week for 6 weeks.Changes in self-rating anxiety scale(SAS),self-rating depression scale(SDS),and quality of life core scale(QLQ-C30)scores were compared among the four groups.Results Before treatment,there were no significant differences in SAS,SDS,or QLQ-C30 subscale scores among the four groups(P>0.05).After treatment,SAS and SDS scores decreased,while QLQ-C30 subscale scores increased in all four groups(P<0.05).After treatment,inter-group comparisons showed significant differences in SAS,SDS,and QLQ-C30 subscale scores(P<0.05),with the combined therapy group showing the best efficacy.The SAS and SDS scores in the five-element music group,sandplay therapy group,and combined therapy group were lower than those in the control group,while QLQ-C30 subscale scores were higher(P<0.05).No significant differences were observed between the five-element music group and sandplay therapy group in SAS,SDS,or QLQ-C30 subscale scores(P>0.05).The combined therapy group had significantly lower SAS and SDS scores and higher QLQ-C30 subscale scores than the five-element music group and sandplay therapy group(P<0.05).Conclusion Five-element music com-bined with sandplay therapy can significantly improve negative emotions and quality of life in patients with malignant tumors.

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Objective:To explore the clinicopathological and molecular genetic characteristics of anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC), including a rare case with the TPM1-ALK gene subtype.Methods:Three cases of ALK-rearranged RCC diagnosed in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2020 to December 2024 were collected. Their clinical pathological and next-generation sequencing (NGS) data were analyzed. Relevant literature was also reviewed, and follow-ups were carried out.Results:Among the three patients, there were 1 female (case 1) and 2 males (cases 2 and 3), with the ages of 29,41 and 44 years, respectively. All of them were presented with space-occupying renal lesions. Case 1 (KIAA1217-ALK RCC) showed mixed cystic and solid components under the microscope, with tubular, papillary, and cribriform arrangements. The tumor cells had clear boundaries, and were cubic or low columnar, arranged in a single layer, pseudostratified or in sheets. The cytoplasm was abundant and eosinophilic, and part of the cytoplasm was vacuolated, as if there was accumulation of mucoid substances. The tumor cell nuclei were oval with prominent nucleoli. A large amount of mucus and inflammatory cell infiltration were noted in the stroma. Case 2 (TPM1-ALK RCC) showed a papillary growth pattern, with small, slender papillae accompanied by branches. The cells were arranged in a single layer, and the cytoplasm was either eosinophilic or clear. Foamy cells were aggregated in the stroma, accompanied by psammoma body-like calcifications. Case 3 (EML4-ALK RCC) was characterized by papillary and tubulocystic structures. The cytoplasm was abundant and eosinophilic. The tumor cell nuclei were large, with prominent nucleoli. There was conspicuous infiltration of lymphocytes and neutrophils in the fibromuscular stroma. The tumor cells all expressed epithelial markers, PAX8, GATA3, P504s and FH. ALK (5A4) staining showed diffuse strong expression in the cytoplasm, while TFE-3 was positive (nuclear stain) only in case 1 and case 3. The fluorescence in situ hybridization showed that ALK gene rearrangement was present in all three cases, while TFE-3 gene rearrangement/mutation was not detectable in case 1 and case 3. NGS showed the KIAA1217::ALK fusion (the fusion site in the exon 11 of KIAA1217 and exon 18 of ALK) in case 1, the TPM1::ALK fusion (the exon 8 of TPM1 and exon 20 of ALK) in case 2, and the EML4::ALK fusion (the exon 2 region of EML4 and the exon 20 region of ALK) in case 3.Conclusions:ALK-rearranged RCC has unique molecular characteristics. Its histological morphology is easily confused with that of papillary RCC and TFE3-rearranged RCC. Both immunohistochemistry and gene rearrangement tests should be used to confirm the diagnosis.

OBJECTIVE: To observe the effect of acupuncture at "four pharyngeal points" on simple vocal tics with liver hyperactivity disturbed wind in children. METHODS: Sixty children with simple vocal tics of liver hyperactivity disturbed wind were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The control group was given Changma Xifeng tablets orally, 3 times a day, while the observation group was treated with acupuncture at "four pharyngeal points" on the basis of the treatment in the control group, 15-20 min a time, once daily for 7 days, with a 3-day break. Both groups were treated for 3 months. The TCM syndrome score and Yale global tic severity scale (YGTSS) score of the two groups were observed before treatment and after 1, 2, 3 months of treatment, the disappearance time of simple vocal tics was recorded, and the therapeutic efficacy was evaluated after treatment. RESULTS: After 1, 2, 3 months of treatment, the TCM syndrome scores and YGTSS scores of the two groups were decreased compared with those before treatment (P<0.01, P<0.05), and the scores of the observation group were lower than those in the control group (P<0.05, P<0.01). The disappearance time of simple vocal tics in the observation group was earlier than that in the control group (P<0.05). The effective rate of the observation group was 93.1% (27/29), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "four pharyngeal points" could improve symptoms in children with simple vocal tics of liver hyperactivity disturbed wind, and shorten the disappearance time of simple vocal tics.
Humans ; Male ; Acupuncture Points ; Female ; Child ; Acupuncture Therapy ; Drugs, Chinese Herbal/administration & dosage* ; Child, Preschool ; Liver/drug effects* ; Tics/drug therapy* ; Treatment Outcome

BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.

Objective Mendelian randomization was used to analyze the causal association between 20 serum metabolites and the risk of ovarian cancer.Methods The gene variations of 20 serum metabolites were obtained from the MRC IEU database as tool variables reflecting exposure levels,while gene variations of ovarian cancer patients were used as instrumental variables reflecting outcome levels.The ovarian cancer dataset ieu-a-1120 included 66,450 European women samples(of which 25,509 were ovarian cancer),and the dataset ieu-a-1228 included 54,990 European women samples(of which 14,049 were ovarian cancer).Two-sample two-way Mendelian randomization analysis was performed on both datasets.This study used inverse variance-weighted(IVW),weigh-ted median method,MR-Egger regression,and combined various analysis methods such as simple mode,and weighted mode.The caus-al effects of 20 metabolites and the risk of ovarian cancer were analyzed.Cochran's Q test was used to perform sensitivity analysis and to verify the reliability of the results.MR Egger intercept test was used to assess the horizontal pleiotropy of tool variables,and use the leave-one-out method to assess whether there were single nucleotide polymorphisms(SNPs)in the results that might have a potential impact on the incidence of ovarian cancer.Finally,the effects of uridine on ovarian cancer cells were verified through cell proliferation and apoptosis experiments.Results The results showed a negative correlation between uridine and the occurrence of ovarian cancer,with statistically significance(ieu-a-1228:P=0.025;ieu-a-1120:P=0.017).MR-Egger regression analysis confirmed the sensitiv-ity and robustness of the analysis results.The CCK8 assay confirmed that uridine inhibited the proliferation of ovarian cancer cells in a concentration-dependent manner,and uridine at a concentration of 10 mM significantly promoted apoptosis in SKOV3 cells(P<0.001)and A2780 cells(P<0.001).Flow cytometry analysis showed that after treatment for 24 hours,uridine at a concentration of 10 mM had the strongest pro-apoptotic effect on ovarian cancer cells,which was significant in SKOV3 and A2780 cells(P<0.05 and P<0.001,respectively).Conclusion Uridine is negatively correlated with the risk of ovarian cancer,which lays a theoretical founda-tion for further understanding the pathogenesis of ovarian cancer and optimizing clinical treatment strategies.