Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

OBJECTIVES: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism. METHODS: A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR. RESULTS: The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05). CONCLUSIONS Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.
Child ; Pregnancy ; Humans ; Female ; Polycystic Ovary Syndrome ; Apoptosis ; Granulosa Cells ; Lipid Metabolism ; Membrane Proteins ; Receptors, Progesterone

It was widely believed that disorders of circadian system were caused by neurodegenera-tive diseases. With the deepening of research,many scholars believed that disorders of circadian system may affect the occurrence and development of neurodegenerative diseases such as Parkinson's disease. 'Parkinson 's disease' and 'Circadian rhythm' were used as the key words of retrieval performance in the databases such as Pubmed,CNKI,Wanfang and so on,and the papers which were closely related with the theme were select-ed. The epidemiology,etiology and pathogenesis,clinical manifestations and the role of circadian system reg-ulation in PD were reviewed. The results show that the disorders of circadian system could be regulated by bright light therapy,melatonin and stem cell therapy,music therapy,and deep brain stimulation. Based on the theory of time medicine,combining the regulation of circadian system with the classical treatment of PD may provide a new breakthrough point for PD treatment. The disorders of circadian system is expected to be-come a new target for PD therapy.

Objective To investigate the expressions and correlations of Kiss-1 and matrix metalloproteinases-9 (MMP9) proteins in the colorectal cancer (CRC) tissues of patients with synchronous colorectal liver metastasis (SCRLM),and the association with the clinicopathologic factors and prognosis of patients.Methods The retrospective case-control study was adopted.The clinicopathological data of 96 patients with SCRLM and 69 patients with CRC and no metastasis who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2000 to May 2013 were collected.The 96 CRC tissues and 50 adjacent normal tissues (distance from resection margin ≥ 5 cm) were collected from 96 patients with SCRLM,and 69 CRC tissues were collected from 69 patients with CRC and no metastasis.Expressions of Kiss-1 and MMP9 protein were detected by immunohistochemistry (IHC).The follow-up of outpatient examination and telephone interview was performed to detect survival of patients till August 2014.Comparison of count data and correlation between expressions of Kiss-1 or MMP9 protein and clinicopathological factors were analyzed by the chi-square test and Fisher exact probability.Survival curve was drawn using the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Correlation analysis was done by the Pearson correlation.Results Expression of Kiss-1 protein was located in the cytoplasm of tissue cells.The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 24.0％ (23/96),43.5％ (30/69) and 52.0％ (26/50),respectively,with a significant difference among the 3 tissues (x2 =14.307,P ＜ 0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2 =0.845,P ＞ 0.05).The positive expression rate of Kiss-1 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =0.702,11.594,P ＜ 0.05).Expression of MMP9 protein was located in the cytoplasm of tissue cells.The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 67.7 ％ (65/96),62.3 ％ (43/69) and 36.0％ (18/50),respectively,with a significant difference among the 3 tissues (x2=14.203,P ＜0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2=8.038,P ＞ 0.05).The positive expression rate of MMP9 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =13.475,13.475,P ＜ 0.05).The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM were 66.7％,21.9％ and 17.6％ in the high-,mederate-and low-differentiated tumor,50.0％,28.6％ and 17.5％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 16.9％ in patients with and without lymph node metastasis,respectively,showing significant differences among the tumor differentiation degree,depth of tumor invasion and lymph node metastasis (x2=6.546,6.172,7.453,P ＜0.05).The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM were 25.0％,66.7％ and 76.2％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 76.1％ in patients with and without lymph node metastasis,respectively,showing significant differences between the depth of tumor invasion and lymph node metastasis (x2 =12.094,8.690,P ＜ 0.05).All the 96 patients with SCRLM were followed up for a median time of 68 months (range,12-176 months).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,26 months,69.6％ and 26.1％ in patients with SCRLM and positive expression of Kiss-1 protein and 26 months,19 months,24.7％ and 12.3％ in patients with SCRLM and negative expression of Kiss-1 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=16.578,14.436,P ＜ 0.05).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,19 months,24.6％ and 12.3％ in patients with SCRLM and positive expression of MMP9 protein and 28 months,16 months,58.1％ and 22.6％ in patients with SCRLM and negative expression of MMP9 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=14.073,8.532,P ＜0.05).Of 96 patients with SCRLM,there were 23 patients with positive expression of Kiss-1 protein (10 with positive expression of MMP9 protein and 13 with negative expression of MMP9 protein) and 73 with negative expression of Kiss-1 protein (55 with positive expression of MMP9 protein and 18 with negative expression of MMP9 protein),with a negative correlation between expressions of Kiss-1 protein and MMP9 protein (r =-0.291,P ＜ 0.05).Conclusions The reduced expression of Kiss-1 protein and elevated expression of MMP9 protein are closely associated with invasion and metastasis of CRC and prognosis of patients.A combination detection of Kiss-1 and MMP9 proteins is expected to become a marker for predicting the prognosis of patients with SCRLM based on the negative correlation between them.

Objective To synthesize podo-and epipodo-podophyllotoxin labeled with 11C and investigate their biodistribution in mice bearing EMT6 tumor by microPET.Methods 11 C-podo-or epipodopodophyllotoxin was synthesized by 11 C-CH3-Triflate mixed with 4'-methyl-demethmyl-podophyllotoxin (podo-and epipodo-) and purified using HPLC.The radiochemical purity (RCP) was analyzed by HPLC.Thirty mice bearing EMT6 tumor were divided into 2 groups and injected with 3.7 MBq 11C-podo-or epipodo-podophyllotoxin.The biodistribution of 11C-podo-or epipodo-podophyllotoxin was evaluated with microPET.The ID％/g was calculated.Paired t test was used to analyze the data.Results The yields of 11C-podo-and epipodo-podophyllotoxin were both ＞90％.The RCP was ＞99％.The biodistribution of 11C-podo-and epipodo-podophyllotoxin was similar with slow blood clearance and high uptake in abdomen.The tumor uptake of 11C-epipodophyllotoxin and 11C-podophyllotoxin at 30 min was (3.63±0.98) ％ID/g and (3.16±0.27) ％ID/g,respectively.The uptake ratio of tumor to blood and to muscle was 0.68 vs 0.62 and 1.52 vs 1.22,respectively.There was no significant difference between the tumor uptake of the two agents (t=0.47,P＞0.05).The result of microPET imaging was consistent with that of mice experiment.Conclusion 11C-podophyllotoxin has limited clinical value for tumor imaging.

Purpose To evaluate the breast imaging reporting and data system (BI-RADS) of ultrasound and 18F-lfuorodeoxyglucose (FDG) PET/CT in diagnosis of breast tumor, and to analyze the correlation between them. Materials and Methods 18F-FDG PET/CT images and ultrasound images of 103 patients with suspected breast cancer were retrospectively analyzed to get correlation between the maximum standardized uptake values (SUVmax) and BI-RADS. Sensitivity, speciifcity, positive predictive value, negative predictive value were compared with histology or follow-up results as golden standard. Results Of the 103 lesions, 46 were benign and 57 were malignant. Pearson correlation coefifcient was 0.464 (P<0.01). The sensitivity, speciifcity, positive predictive value, and negative predictive value of PET/CT were 89.47%, 73.91%, 80.95%and 84.99%, respectively;those of BI-RADS were 94.70%, 69.60%, 79.42%and 91.38%, respectively. The sensitivity, speciifcity, positive predictive value, and negative predictive value in patients with BI-RADS 3-4 were 88.90%, 71.40%, 66.65%, and 90.91%, respectively. The sensitivity, speciifcity, positive predictive value, and negative predictive value for BI-RADS grading diagnosis were 88.90%, 46.40%, 51.60%and 86.67%, respectively. Conclusion There is no signiifcant correlation between SUVmax and BI-RADS. BI-RADS has low speciifcity for patients with BI-RADS grade 3-4, while PET/CT can make up this shortcoming. Combined diagnosis in the breast disease can be potentially recommended in clinics.

This retrospective investigation was directed to the applicability of Radial Basis Function Neural Network (RBF-NN) and Discriminant Analysis in the grading of gliomas. The data on 116 patients with primary glioma in our hospital from February 2008 to April 2009 were collected. Kruskal-Wallis H test was used to draw in the variable age ranks and then to take them out from the range of different grades of gliomas. The results of RBF-NN model, discriminant analysis, and the combined model of RBF-NN and discriminant analysis were evaluated and compared respectively with and without age. In this study, different classifications of gliomas showed statistically significant differences in age: and the accuracy of the models with age was better than the ones without age. The predictive accuracy and Kappa value of RBF-NN model and the combined model were also better than those exhibited by Bayes discriminant analysis. Consequently, as a prediction model, or to help other models, RBF-NN is of significance to predicting the grade of gliomas.
Brain Neoplasms ; pathology ; Glioma ; pathology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Neoplasm Grading ; Neural Networks (Computer)

Background and purpose: Astrocytoma is the most common neuroepithelial neoplasm, and its grading has profound effect on its treatment and prognosis. To investigate the application of stepwise discriminant analysis in grading astrocytomas, this study developed two models of stepwise discriminant analysis according to relevant factors of astrocytoma. Methods: From January 2008 to April 2009, 111 primary astrocytoma patients were enrolled. Each patient was scored based on location, signal intensity on T1WI, signal intensity on T2WI, enhancement, edema, border, cyst or solidness, and mass effect of their magnetic resonance images. With their age score of grading, Fisher stepwise discriminant analysis and the Logistic discdminant were used. The results from the two models were then evaluated and compared. Results: According to Fisher stepwise diseriminant analysis, the predictive accuracy was 87.7% with 80.0% sensitivity, 91.5% specificity and 0.942 area of ROC curve. However, the predictive accuracy of Logistic discriminant analysis was 84.9% with 80.0% sensitivity, 86.8% specificity and 0.940 area of ROC curve. There were no statistically significant differences in terms of accuracy (P=0.250) and areas under ROC curve (Z=0.433, P=0.665) between the two models. Conclusion: Two stepwise discriminant analysis models are meaningful to predict the grading of astrocytoms, and the application of Fisher stepwise discriminant analysis is simpler than the Logistic discriminant analysis.