OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective:To investigate the relationship between life events, cognitive emotional regulation strategies, neuroticism and depression in pregnant women and the internal mechanism of action.Methods:Short-term longitudinal follow-up design were used in this study.A total of 327 pregnant women in the third trimester of pregnancy were investigated with pregnant women's life events scale, cognitive emotion regulation strategy questionnaire, neuroticism subscale of Chinese big five personality questionaire-short form at T1 time point, and patient health questionnaire 9 were measured after 6 weeks(T2).SPSS 20.0 macro program PROCESS was used to examine the mediating effect of cognitive emotion and the moderating effect of neuroticism.Results:(1) The incidence of depression in the third trimester pregnant women was 12.23%.(2)There was significant positive correlation between the total score of life events in pregnant women(T1) and the total score of non-adaptive cognitive emotional regulation strategies(T1) ( r=0.25, P<0.01).Total neurotic personality(T1) and total depressive mood(T2) were significantly positively correlated ( r=0.46, P<0.01).The total scores of life events(T1) of pregnant women were significantly positively correlated with the total scores of depression(T2) ( r=0.36, P<0.01).(3) The non-adaptive cognitive emotion regulation strategy (T1) played a partial mediating role between life events (T1) and depression (T2).The direct effect (effect size=0.29) and the mediating effect (effect size=0.07) accounted for 80.55% and 19.44% of the total effect (effect size=0.36).(4) Neuroticism regulates the second part of the mediating effect of the mediating model.Specifically, the higher the level of individual neuroticism, the stronger the positive predictive effect of non-adaptive cognitive emotion regulation strategies on maternal depression. Conclusion:Pregnant life events play a role in maternal depression through the mediating role of non-adaptive cognitive emotional regulation strategies and the moderating role of neuroticism.

OBJECTIVE： To study the vasodilatory effect of oxysophocarpine （OSC） on isolated thoracic aortic rings of rats and its possible mechanism. METHODS： Thoracic aortic rings of rats were collected （called “vascular ring” for short）. Using K-H nutrient solution as blank control and the diastolic rate as index， the effects of different concentrations （0.2-1.0 mg/mL） of OSC on normal vascular rings in basal state， normal or endothelium-free vascular rings pre-contracted by norepinephrine （PE， 1×10－6 mol/L） were investigated. After pre-culturing normal thoracic aortic rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester（L-NAME）and cyclooxygenase inhibitor indomethacin（INDO），as well as pre-culturing endothelium-free vascular rings by potassium ion channel blocker BaCl2，tetraethylammonium（TEA）and 4-aminopyridine（4-AP）， the diastolic effects of OSC of different concentrations （0.2-1.0 mg/mL） on the above vascular rings were investigated by using the same method. RESULTS： Compared with blank control， there was no significant effects of different concentrations of OSC on the diastolic rate of normal vascular rings in basal state （P＞0.05）， but 0.4-1.0 mg/mL OSC could significantly improve the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＜0.01）， in concentration-dependent manner. After preculturing with L-NAME， INDO， 4-AP and BaCl2， different concentrations of OSC had no significant effect on the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＞0.05）. After pre-culturing with TEA and Gli， 0.4-1.0 mg/mL OSC could significantly reduce the diastolic rate of endothelium-free vas- cular rings pre-contracted by PE （P＜0.01）. CONCLUSIONS： OSC did not significantly dilate the thoracic aortic rings of rats in the basal state within the dose range （0.2-1.0 mg/mL）， but OSC of 0.4-1.0 mg/mL have significant diastolic effects on the normal or endothelium-free thoracic aortic rings of rats pre-contracted with PE. The mechanism of thoracic aortic rings dilation is endothelium-independent， which may be associated with receptor operational calcium channel，Ca2+-activated potassium channels and ATP-sensitive potassium channels.

Objective To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) at admission for large vessel occlusion (LVO) in patients with acute ischemic stroke. Methods The clinical data of patients with acute ischemic stroke admitted to Guangzhou First People's Hospital from January 2016 to November 2017 were enrolled retrospectively. NLR was calculated according to results of blood routine examination within 6 h after admission. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and LVO. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for LVO. Results A total of 109 patients with acute ischemic stroke were enrolled, including 42 females (38. 5％) and 67 males (61. 5％). Their mean age was 63. 6 years. Forty-six patients (42. 2％) had LVO. The proportions of patients with atrial fibrillation, previous stroke or transient ischemic attack, and the National Institutes of Health Stroke Scale score, white cell count, NLR, neutrophil count, and fasting blood glucose in the LVO group were significantly higher than those in the non- LVO group, while lymphocyte count was significantly lower than that in the non-LVO group (all P < 0. 05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for LVO after adjusting for the confounding factors (odds ratio 2. 768, 95％ confidence interval, 2. 272-4. 984; P = 0. 001). The ROC curve analysis of NLR predicting LVO showed that the area under the curve was 0. 712 (95％ confidence interval 0. 638-0. 793), and the sensitivity and specificity were 79. 3％ and 73. 6％ respectively as the optimal cut-off value was 4. 18. Conclusions Increased NLR in early peripheral blood may effectively predict LVO in acute ischemic stroke.

ObjectiveTo evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism.Methods A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluationⅡ (APACHEⅡ) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment.Results There was no statistically significant difference in APACHEⅡ score before treatment between two groups, however, the APACHEⅡ scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70,P< 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (allP> 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L):1.12±0.11 vs. 1.35±0.14, SCr (μmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01,PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P< 0.05 orP< 0.01].ConclusionXuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.