Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy

ObjectiveThe expression and significance of interleukin(IL)-17 in a murine model of experimental systemic sclerosis(SSc) was studied and its correlation with transforming growth factor-beta 1 (TGF-β1) was explored.Methods Thirty female BALB/c mice were randomly divided into 3 groups,including a control group, bleomycin(BLM) injection for 4 weeks group(model 1 group) and a termination injection of BLM 4 weeks group(model 2 group).The pathological changes of skin and lung were detected.The mRNA expressions of IL-17A,RORγt,TGF-β1 mRNA were evaluated by real-time PCR.Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and TGF-β1 in the serum and bronchoalveolar lavage fluid(BALF).Comparisons among groups were performed by variance analysis.ResultsSkin and lung of the model groups showed evident inflammatory cell infiltration and increased deposition of collagen fibers.The score of dermal inflammation and lung fibrosis was significantly higher in the model 1 and model 2 groups (2.5±0.8,3.0±1.8), (2.4±0.8,3.1±1.2) as compared to that of the control group (0.9±0.7,0.9±1.0),(F=12.19,8.367,25.11,4.641; all P＜0.05).The amount of hydroxyproline was markedly increased in the model groups than in the control group.Compared with those of the control group,the mRNA levels of IL-17A,RORγt,TGF- 31 in the skin and lung of the model 1 group were higher.The levels of IL-17 in serum and BALF of the model 1 group was significantly increased and the levels of TGF- β1 were increased in BALF and decreased in the serum (all P＜0.05).The mRNA levels of IL-17A in skin and lung had a positive correlation with the mRNA levels of TGF- β1,score of dermal inflammation and lung fibrosis.The levels of IL-17 in serum had a positive correlation with hydroxyproline of the skin and lung.ConclusionIL-17 may participate in systemic immune-mediated inflammation and changes of skin and lung in SSc and when combined with TGF-β1 togetter will cause damage to skin and lung in SSc.

Objective:To identify proteins associated with nasopharyngeal carcinoma (NPC) metastasis,and provide scientific basis for the prevention and cure of NPC.Methods:A two-dimensional gel electrophoresis and mass spectrometry were performed to screen for differential proteins between highly metastatic 5-8F and non-metastatic 6-10B NPC cell lines.Western blot was used to confirm the differential proteins.We used siRNA to inhibit the expression of differential protein nm23-H1 to determine the association of nm23-H1 with NPC in vitro invasive ability.Immunohistochemistry and statistics were used to evaluate the correlation of nm23-H1 expression with clinicopathological features and clinical outcomes in paraffin-embedded archival tissues including 93 cases of primary NPC and 20 cases of cervical lymphonode metastatic NPC (LMNPC).Results:A total of 15 differential proteins in the 2 cell lines were identified by a proteomic approach,and 3 differential proteins were selectively confirmed.Downregulation of nm23-H1 by siRNA significantly increased the in vitro invasive ability of 6-10B.Significant nm23-H1 downregulation was observed in LMNPC compared with primary NPC.nm23-H1 downregulation in primary NPC was positively correlated with lymphonode and distant metastasis,advanced clinical stage and recurrence.Survival curves showed that patients with nm23-H1 downregulation in primary NPC had a poor prognosis.Multivariate analysis confirmed that nm23-H1 expression level in primary NPC was an independent prognostic indicator.Conclusion:nm23-H1 behaves as a metastasis suppressor in NPC,and nm23-H1 downregulation is a biomarker for poor NPC prognosis.

Objective To improve the diagnostic and therapeutic levels for spontaneous spinal epidural hematoma(SSEH) by summarizing the effect of microsurgery and clinical diagnosis of SSEH. Methods The therapeutic efficacy of 21 patients with SSEH undergoing microsurgery from March 1996 to March 2003 was retrospectively analyzed. Results On discharge from hospital, muscle strength of the bilateral lower extremities of 13 patients was restored to grades Ⅲ or Ⅳ, 5 to grade Ⅴ but no change was found in 3 patients. Conclusion Early diagnosis of SSEH and surgical treatment are helpful to restoring the function of the injured spinal cord and decrease of sequelae.

Objective To investigate the roles of endoscopic biopsy and third ventriculostomy in the diagnosis and treatment of pineal region tumors in children. Methods Endoscopic biopsy and third ventriculostomy were performed in 9 pediatric patients with pineal region tumors. Results Successful third ventriculostomy, confirmed by MRI, was performed in 9 cases of children with obstructive hydrocephalus. No complications were found in all patients. Conclusion Endoscopic biopsy and third ventriculostomy are effective neuroendoscopic procedures in minimally invasive preferential management of pineal region tumors.