ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Objective:To investigate the application value of the maximum standardized uptake value (SUVmax) of 18F prostate-specific membrane antigen (PSMA) PET/CT combined with the minimum apparent diffusion coefficient (ADCmin) of biparametric magnetic resonance imaging (bpMRI) in predicting pathological upgrading after radical prostatectomy (RP) for prostate cancer. Methods:The data of 89 patients with localized prostate cancer treated at Beijing Hospital from April 2019 to October 2023 were retrospectively analysed. The average age of patients was (68.4±7.0) years old, with prostate-specific antigen (PSA) level of 7.7 (5.4, 12.9) ng/ml, prostate volume of 34.6 (26.9, 47.1) ml, tumor diameter of 1.3 (1.0, 1.8) cm, prostate imaging reporting and data system(PI-RADS) score of 5 in 29 cases (32.6%), clinical stage ≥T 3 in 13 cases (14.6%). There were 31 cases (34.8%) in group 1 of targeted biopsy International Society of Urological Pathology (ISUP)grading groups, 36 cases (40.4%) in group 2, 11 cases (12.4%) in group 3, and 11 cases (12.4%) in group 4. All patients underwent 18F-PSMA PET/CT and bpMRI examinations before RP. The index lesion, identified as the highest Gleason score in pathological whole-mount sections, were outlined. SUVmax and ADCmin values were calculated from the images' region of interest. Pathological upgrading was defined as the post-RP grade group higher than the targeted-biopsy grade group. Clinical data of patients with and without pathological upgrading were compared. Spearman correlation coefficient analysis was used to assess the correlation between SUVmax and ADCmin. Multivariate logistic regression analysis was conducted to evaluate the factors influencing pathological upgrading. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of each indicator for pathological upgrading. Results:Among the 89 cases, 31 cases (34.8%) experienced pathological upgrading. Compared with the patients without pathological upgrading, the SUVmax [11.3 (8.1, 16.4) vs. 6.7 (4.6, 9.2)], SUVmax/ADCmin ratio [3.1 (2.0, 4.6) vs. 1.4 (0.9, 2.1)], PSA [9.8 (6.3, 15.6) ng/ml vs. 7.1 (5.1, 10.5) ng/ml], PSA density [0.3 (0.2, 0.5) ng/ml 2 vs. 0.2 (0.1, 0.3) ng/ml 2], and post-RP ISUP grade group [≥3 group 17 cases (54.8%) vs. 13 cases(22.4%) ]were higher in patients with pathological upgrading, while ADCmin [3.8 (3.0, 5.3) ×10 -4 mm 2/s vs. 5.2 (3.6, 6.1)×10 -4 mm 2/s] and targeted biopsy ISUP grade group [≤2 group 27 cases(87.1%) vs. 40 cases(69.0%) ] were lower (all P<0.05). Spearman analysis showed a negative correlation between SUVmax and ADCmin ( R = -0.227, P = 0.032). Multivariate logistic regression analysis revealed that SUVmax ( OR = 1.108, 95% CI 1.020-1.238), ADCmin ( OR=0.607, 95% CI 0.390-0.874), and SUVmax/ADCmin ratio ( OR = 1.815, 95% CI 1.282-2.949) independently predicted pathological upgrading. The AUC of the SUVmax/ADCmin ratio for predicting pathological upgrading (AUC = 0.817) was higher than that of SUVmax (AUC = 0.774) and ADCmin (AUC=0.686), indicating a higher predictive efficiency. Conclusions:SUVmax, ADCmin, and SUVmax/ADCmin ratio can independently predict pathological upgrading in targeted biopsy of prostate cancer. The SUVmax/ADCmin ratio has a stronger predictive value for pathological upgrading.

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

OBJECTIVE: To investigate the mechanism of miRNA-340 for regulating the proliferation of gastric cancer (GC) cells and predict its interacting circular RNAs (circRNAs), its downstream target genes and the involved signaling pathways. METHODS: The differentially expressed miRNAs in GC cell lines were analyzed and screened using miRNA microarrays. The expression level of miRNA-340 in 21 pairs of GC tissues and adjacent normal tissues was detected using real-time PCR. MTT and EdU assays were performed to examine the effect of miRNA-340 on the proliferation ability of HFE145 and BGC-823 cells. We also tested the effect of miRNA-340 inhibition on subcutaneous tumorigenesis of GC cells in a nude mouse model. The downstream target genes of miRNA-340 and the probable signal pathways were predicted online using Targetscan and DAVID database, respectively. The interacting circRNAs of miRNA-340 were analyzed using starBase platform. RESULTS: Among the differentially expressed miRNAs, miRNA-340 was significantly down-regulated in GC cell lines. Real-time PCR results showed that the expression of miRNA-340 was significantly lower in GC tissues than in the adjacent tissues ( < 0.05). MTT and EdU cell proliferation assays showed that miRNA-340 overexpression inhibited the proliferation of GC cells in vitro. In the nude mouse models, the proliferation of GC cells transfected with miRNA-340 inhibitor was obviously enhanced. Bioinformatics analysis suggested that miRNA-340 had 21 target genes with 3 or more conserved sites, and these genes were involved in tumorigenesis and invasion. The top 10 circRNAs were selected as the most powerful sponge circRNAs interacting with miRNA-340. CONCLUSIONS miRNA-340 may play the role of a tumor suppressor in tumorigenesis and progression. Overexpression of miRNA-340 suppress the proliferation of GC cells, suggesting its involvement in the development of GC along with multiple circRNAs.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Computational Biology ; Gene Expression Regulation, Neoplastic ; Mice ; MicroRNAs ; Stomach Neoplasms

Objective To compare prenatal ultrasonography and MRI in view of the accuracy in the diag-nosis of congenital cystic adenmatiod malformation(CAMM)of the lung. Methods From January 2014 to Octo-ber 2015,68 fetus who were examined with both prenatal ultrasonography and MRI and diagnosed as CAMM by pathological findings after operation or autopsy in our study. Taking the final pathological diagnosis of fetal CCAM genotyping as the gold standard,the accuracy of prenatal ultrasonography and MRI were compared in the diagnosis of CAMM of the lung.P<0.05 was considered as statistically significant. Results The alignment degree of prena-tal ultrasound in the diagnosis of CAMM was significantly larger than that of MRI examination to the pathological di-agnosis.Conclusion Prenatal ultrasound is an important method for diagnosing CCAM before pregnancy with high accuracy and affordability.

Objective To explore the clinical pathological characteristics of breast solid papillary carcino-ma(SPC). Methods The clinical manifestation,pathology morphology,immunohistochemical characteristics and prognosis of 23 cases with SPC was reviewed. Results There were 16 cases with nipple discharge as the chief com-plaint while 7 cases were mass. 10 cases of ultrasonic examination showed 6 cases(60%)were above BI-RADS grade 4 while 8/13 in X-ray examination. In 8 cases of SPC with invasion,5 cases were luminal A and 3 cases were lumi-nal B. There were no significant differences in the mean age,mean diameter of the mass,neuroendocrine markers (CgA and Syn)and proliferation marker Ki67 between in situ SPC group and invasive SPC group(P > 0.05). The difference between P63 and CK5/6 was statistically significant(P = 0.001,P = 0.019). No recurrence was found in 21 patients. Conclusions SPC is a rare type of breast cancer with good prognosis. Imaging and ductosco-py are easy to make under-diagnosis while pathology is likely to make misdiagnosis,therefore clinical pathologists should pay more attention so as to treat it more accurately.

Objective To determine the incidence and clinical features of headache after carotid endarterectomy (CEA).Methods A retrospective analysis was made on the data of patients undergoing CEA in the Department of Vascular Surgery,Peking Union Medical College Hospital from Jan 2014 to Jan 2015.There were 119 males and 24 females,including 97 cases of symptomatic carotid stenosis and 110 cases of severe carotid stenosis.Results The incidence of newly emergent headache after surgery was 44％ (63/143).The earliest time of headache was 30 minutes after surgery and the latest was 6 days after surgery.95％ of headache occurred within 48 hours after surgery (60/63).79.4％ (50/63) of the headache lay ipsilaterally with CEA,and bilateral headache accounted for 20.6％ (13/63).Severe headache accounted for 4.8％ (3/63),all were ipsilaterally frontal and temporal headache,complicating central nervous system symptoms.Conclusions After CEA headache is a common clinical symptom.Most were mild to moderate and unilateral,which can be relieved spontaneously.Cerebral hemodynamics need to be further examined to differentiate the different pathological states of severe headache on the operative side after CEA because of the high risk of developing hyperperfusion syndrome or cerebral infarction.History of TIA or stroke is the risk factor of post-CEA headache.

Ojective To explore the effect of the hydroxyapatite(HAp)and gelatin(Gel)coating on the healing of the polyethylene terephthalate(PET)artificial ligament.Methods The artificial ligaments were divided into a PET group with a pure PET surface and a PET/HAp/Gel group coated with HAp and Gel.Both coatings were observed using the scanning electron microscope(SEM).Forty-eight male New Zealand rabbits were randomly divided into two groups and underwent anterior cruciate ligament reconstruction,before two kinds of artificial ligaments were implanted respectively.Four weeks and 8 weeks after the operation,the rabbits were sacrificed,and histological hematoxylin and eosin (HE)staining as well as the biomechanical examination were performed.Results HAp/Gel coating was found depositing on the surface of PET artificial ligaments.Histological HE staining showed a thick fibrous connective tissue forming at the graft-host bone interface 4 weeks postoperatively,and the interface width of both groups were narrowed,with significantly more shrinking in the PET/HAp/Gel coating group.And new bone tissues were found in the interface of PET/HAp/Gel group 8 weeks after the operation.The biomechanical examination found significant differences in the failure load between the PET(46.16 ± 2.88 N) and PET/HAp/Gel group(71.32 ± 3.92 N)8 weeks after the surgery(P=0.0021).And 4 weeks and 8 weeks after the surgery,significant differences were found in the stiffness between the PET group and the PET/HAp/Gel group(11.06 ± 1.14 N/mm vs 16.20 ± 1.17 N/mm,P=0.0199;14.37 ± 0.88 N/mm vs 24.35 ± 1.35 N/mm,P=0.0008).Conclusion HAp/Gel coating can enhance the osteogenesis of PET artificial ligaments,promoting the new bone formation at the graft-host bone interface and herein strengthening the graft-host bone healing.

Objective To explore the changes in gene expression and biological process of the osteoarthritis (OA) induced by anterior cruciate ligament (ACL) transection and partial medial meniscectomy,so as to provide bioinformatic basis for further studying the molecular mechanism of OA.Methods The gene chip datasets of a rat model of early 0A induced by ACL transection and partial medial meniscectomy were downloaded from GEO databases (submitted by Appleton,et al.).The differential expression genes (DEGs)were identified,and the Gene ontology(GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEGs were conducted using bioinformatic methods.Results A total of 170 DEGs including 97 up-regulated genes and 73 down-regulated genes were identified.The up-regulated genes were mainly enriched in the extracellular matrix (ECM) and were closely related to the ECM-receptor interaction,while the down-regulated genes were mainly enriched in the biological function of muscle contraction and were linked with the peroxisome proliferators-activated receptor (PPAR) signaling pathway.Conclusion The changes of ECM and muscle contraction play a key role in the occurrence and development of OA.The ECM-receptor interaction and PPAR signaling pathway are strongly associated with OA and worthy of further study.

Objective To retrospectively investigate the disease spectrum of inpatients aged over 65 year and cost constitution in Sichuan Provincial People's Hospital from 2010 to 2014,so as to provide baseline data for further study.Methods The inpatients'disease spectrum and costs were collected from hospital information system.The diseases were classified according to the International Classification of Diseases(ICD-10).The data were analyzed using SPSS 18.0 software.Results The total number of old inpatients was 111,935,and male (55.2 ％) was more than female (44.8 ％).The average age was (74.5 ±6.8)years.The top four systematic diseases of primary diagnosis were circulatory system disease (21.0 ％),respiratory system disease (13.7 ％),digestive system disease (12.7％)and neoplasms (12.1％).The total number of male inpatients was more than the female inpatients.The average cost per capita was increased from (￥)18,778.1 yuan to (￥)23,391.9 yuan since 2010.The proportion of all costs accounted for by drugs in elderly inpatients was decreased from 45.5％ to 38.9％ since 2010.Nosocomial infection was decreased from 3.19％ to 0.16％ since 2010.Conclusions The number of elderly inpatients are more in male than in female in Sichuan Provincial People's Hospital from 2010 to 2014.The most common systematic disease is circulatory system diseases,and followed by respiratory system diseases,digestive system diseases and neoplasms.The proportion of all expenditures accounted for by drugs was declined in five years,while the average cost per capita is increased.