Gender differences in the impact of anatomical factors on non-contact anterior cruciate ligament injuries: a magnetic resonance study.

PURPOSE: To identify MRI-detected anatomical risk factors for non-contact anterior cruciate ligament (ACL) injuries across genders. METHODS: A retrospective analysis was performed on 141 ACL-reconstructed patients (35 females, 106 males) and 142 controls (37 females, 105 males) from January 2020 to April 2022. Inclusion criteria were primary non-contact ACL injuries. The tibial plateau slope, lateral femoral condyle index, Insall-Salvati index, and patellar tendon angle were measured, using binary logistic regression for gender-specific risk evaluation. RESULTS: Increased lateral tibial plateau slope, reduced intercondylar notch width index, lateral femoral condyle index, and patellar tendon angle correlated with ACL injuries in both genders. The Insall-Salvati index was a significant risk factor in females but not in males. CONCLUSION: This study identifies the lateral tibial plateau slope, notch width index, lateral femoral condyle index, and patellar tendon angle at near-extension as risk factors for ACL injuries in both genders, with the Insall-Salvati index also implicated in females.

Osteocytic cells exposed to titanium particles increase sclerostin expression and inhibit osteoblastic cell differentiation mostly via direct cell-to-cell contact.

The mechanism underlying induction of periprosthetic osteolysis by wear particles remains unclear. In this study, cultured MLO-Y4 osteocytic cells were exposed to different concentrations of titanium (Ti) particles. The results showed that Ti particles increased expression of the osteocytic marker SOST/sclerostin in a dose-dependent manner, accelerated apoptosis of MLO-Y4 cells, increased the expression of IL-6, TNF-α and connexin 43. SOST silence alleviated the increase of MLO-Y4 cells apoptosis, decreased the expression of IL-6, TNF-α and connexin 43 caused by Ti particles. The different co-culture systems of MLO-Y4 cells with MC3T3-E1 osteoblastic cells were further used to observe the effects of osteocytic cells' changes induced by Ti particles on osteoblastic cells. MLO-Y4 cells treated with Ti particles inhibited dramatically differentiation of MC3T3-E1 cells mostly through direct cell-to-cell contact. SOST silence attenuated the inhibition effects of Ti-induced MLO-Y4 on MC3T3-E1 osteoblastic differentiation, which ALP level and mineralization of MC3T3-E1 cells increased and the expression of ALP, OCN and Runx2 increased compared to the Ti-treated group. Taken together, Ti particles had negative effects on MLO-Y4 cells and the impact of Ti particles on osteocytic cells was extensive, which may further inhibit osteoblastic differentiation mostly through intercellular contact directly. SOST/sclerostin plays an important role in the process of mutual cell interaction. These findings may help to understand the effect of osteocytes in wear particle-induced osteolysis.

Reduction of SOST gene promotes bone formation through the Wnt/ß-catenin signalling pathway and compensates particle-induced osteolysis.

The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO-Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase- (ALP) and osterix-positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3-E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased ß-catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased ß-catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/ß-catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.

Dexamethasone-induced cytotoxicity in human osteoblasts is associated with circular RNA HIPK3 downregulation.

Dexamethasone (DEX) exerts potent cytotoxicity against cultured human osteoblasts. The current study examined the role of the circular RNA HIPK3 (circHIPK3) in the mechanism of cell death. We found that circHIPK3 expression was downregulated in DEX-treated human osteoblasts and circHIPK3 levels decreased in human necrotic femoral head tissues. In OB-6 osteoblastic cells and primary human osteoblasts ectopic overexpression of circHIPK3 potently suppressed DEX-induced apoptosis and programmed necrosis. Conversely, knockdown of circHIPK3by targeted siRNAs enhanced DEX-induced cytotoxicity in human osteoblasts. We further observed that microRNA-124 (miR-124), a key miRNA sponged by circHIPK3, accumulated following DEX treatment in OB-6 cells and primary osteoblasts. Confirming the role of miR-124 in DEX-induced cytotoxicity, miR-124 inhibitor attenuated cell death in human osteoblasts. Conversely, forced overexpression of miR-124 mimicked DEX-induced actions and induced cytotoxicity in human osteoblasts. We conclude that DEX-induced cytotoxicity in human osteoblasts is associated with circHIPK3 downregulation.

LncRNA EPIC1 protects human osteoblasts from dexamethasone-induced cell death.

Dexamethasone (Dex) can induce injury to human osteoblasts. Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) is a novel Myc-interacting LncRNA. Its effect on Dex-treated human osteoblasts is studied here. In OB-6 osteoblastic cells and primary human osteoblasts, treatment with Dex increased expression of Lnc-EPIC1. Its expression is also elevated in the necrotic femoral head tissues of Dex-taking patients. Ectopic overexpression of Lnc-EPIC1 inhibited Dex-induced apoptosis and programmed necrosis in OB-6 cells and primary human osteoblasts. Reversely, Lnc-EPIC1 silencing by targeted siRNA potentiated Dex-induced cytotoxicity. Myc is the target of Lnc-EPIC1 in osteoblasts. Exogenous overexpression of Myc protected OB-6 cells from Dex. Conversely, Myc knockout by CRISPR-Cas-9 method abolished Lnc-EPIC1-induced OB-6 cytoprotection against Dex. Together, Lnc-EPIC1 expression protects human osteoblasts from Dex possible via regulation of Myc.

GLIM criteria represent a more suitable tool to evaluate the nutritional status and predict postoperative motor functional recovery of older patients with hip fracture: A retrospective study.

Early recognition of malnutrition is essential to improve the prognosis of older patients with hip fracture. The Nutritional Risk Screening 2002 (NRS-2002), the Short-Form Mini Nutritional Assessment (MNA-SF) and the Global Leadership Initiative on Malnutrition (GLIM) are widely used in malnutrition diagnosis. However, criteria for predicting postoperative hip joint motor function in older patients with hip fractures are still necessary. The objective of this study was to select the most appropriate criteria from the NRS-2002, the MNA-SF and the GLIM in predicting the postoperative hip joint motor function recovery 1 year after surgery. This retrospective observational study included 161 patients aged ≥ 65 years with hip fractures. The nutritional status of patients was determined by the NRS-2002, MNA-SF and GLIM. The Harris hip joint score (HHS), the primary outcome of this study, was used to evaluate hip joint motor function. HHS was classified as excellent (HHS > 75) or non-excellent outcomes (HHS ≤ 75). Logistic regression models for hip joint motor function recovery were constructed. Both the receiver operating characteristic curve and the decision curve analysis were used to select the most predictive criteria. The overall mean age of the 161 patients was 77.90 ±â€…8.17. As a result, NRS-2002 (OR:0.06, 95%CI [0.01, 0.17]), MNA-SF (OR:0.05, 95%CI [0.00, 0.23]) and GLIM (OR of moderate: 0.03, 95%CI [0.01, 0.11]; OR of severe: 0.02 [0.00, 0.07]) were predictive for recovery of hip joint motor function. Additionally, both the area under curve of the receiver operating characteristic curve (NRS-2002: 81.2 [73.8, 88.6], MNA-SF: 76.3 [68.5, 84.2], GLIM: 86.2 [79.6,92.8]) and the decision curve analysis showed the GLIM was better than others. Compared with NRS-2002 and MNA-SF, GLIM was a more suitable nutritional assessment criteria to predict the postoperative recovery of hip joint motor function for older patients with hip fracture 1 year after surgery.

Uncertainty analysis and optimization of laser thermal pain treatment.

Uncertainty in operating parameters during laser thermal pain treatment can yield unreliable results. To ensure reliability and effectiveness, we performed uncertainty analysis and optimization on these parameters. Firstly, we conducted univariate analysis to identify significant operational parameters. Next, an agent model using RBNN regression determined the relationship between these parameters, the constraint function, and the target function. Using interval uncertainty analysis, we obtained confidence distributions and established a nonlinear interval optimization model. Introducing RPDI transformed the model into a deterministic optimization approach. Solving this with a genetic algorithm yielded an optimal solution. The results demonstrate that this solution significantly enhances treatment efficacy while ensuring temperature control stability and reliability. Accounting for parameter uncertainties is crucial for achieving dependable and effective laser thermal pain treatment. These findings have important implications for advancing the clinical application of this treatment and enhancing patient outcomes.

Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis.

BACKGROUND: The implication of deregulated circular RNAs in osteoporosis (OP) has gradually been proposed. Herein, we aimed to study the function and mechanism of circ_0001825 in OP using osteogenic-induced human-derived mesenchymal stem cells (hMSCs). METHODS: The content of genes and proteins was tested by quantitative real-time polymerase chain reaction and Western blotting. The osteogenic differentiation in hMSCs were evaluated by ALP activity and Alizarin Red staining, as well as the detection of osteogenesis-related markers. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The binding between miR-1270 and circ_0001825 or SMAD5 (SMAD Family Member 5) was confirmed by using dual-luciferase reporter assay and pull-down assay. RESULTS: Circ_0001825 was lowly expressed in OP patients and osteogenic induced hMSCs. Knockdown of circ_0001825 suppressed hMSC viability and osteogenic differentiation, while circ_0001825 overexpression showed the exact opposite effects. Mechanistically, circ_0001825/miR-1270/SMAD5 formed a feedback loop. MiR-1270 was increased and SMAD5 was decreased in OP patients and osteogenic induced hMSCs. MiR-1270 up-regulation suppressed hMSC viability and osteogenic differentiation, which was reversed by SMAD5 overexpression. Moreover, miR-1270 deficiency abolished the effects of circ_0001825 knockdown on hMSCs. CONCLUSION: Circ_0001825 promoted hMSC viability and osteogenic differentiation via miR-1270/SMAD5 axis, suggesting the potential involvement of circ_0001825 in osteoporosis.

The degree of fracture reduction does not compromise the clinical efficacy of arthroscopic reduction and fixation of tibial posterior cruciate ligament avulsion fractures: A retrospective study.

This study aimed to explore the postoperative outcomes of patients who underwent arthroscopic internal fixation with repositioning sutures for the treatment of posterior cruciate ligament (PCL) avulsion fractures with poorly reduced fracture fragments. It was hypothesized that improperly repositioned fracture fragments might not influence the postoperative clinical outcomes in patients with PCL avulsion fractures treated by arthroscopic sutures. From January 2020 to December 2021, patients admitted to our hospital with PCL avulsion fractures were evaluated. Our inclusion criteria were as follows: diagnosis of PCL avulsion fracture as Meyers & McKeever Type II or Type III; underwent arthroscopic double tunnel suture fixation; and age below 70. Of the patients meeting these criteria, data from 34 individuals were collected by a designated follow-up officer. Based on postoperative imaging, the patients were divided into 2 groups: well fracture reduction and poor fracture reduction groups. Prior to the surgery, the Lysholm score, knee mobility, and international knee documentation committee (IKDC score) were recorded for both groups. At the 3-month post-surgery mark, CT-3D reconstruction was performed. Statistical analysis was conducted on the collected data. For data that conformed to a normal distribution, the t test was applied. For data that didn't conform, we used a non-parametric test. Both groups achieved successful wound healing without encountering any adverse events, such as fracture nonunion infection. Fracture healing was observed in both groups at the 3-month postoperative mark. The average follow-up duration was 13.24 ± 6.18 months. There were no significant differences in Lysholm score, IKDC score, or knee mobility between the well- and poorly-reduced groups at the final follow-up (P > .05). Postoperatively, both groups demonstrated significant improvements in knee function compared to the preoperative scores, with statistically significant differences observed in Lysholm score, IKDC score, and knee mobility (P < .05). Arthroscopic fixation with double-tunnel sutures proved to be a highly effective treatment approach for PCL avulsion fractures, even in cases where the fractures were poorly reduced. Remarkably, there were no significant differences observed in postoperative knee function between the well- and poorly-reduced groups, indicating that both groups achieved favorable outcomes.

Left atrial function index predicts poor outcomes in acute myocardial infarction patients treated with percutaneous coronary intervention.

Background and aims: The left atrial function index (LAFI) is an index that combines the left atrial emptying fraction, adjusted left atrial volume and stroke volume. The prognostic value of LAFI in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study aims to determine whether LAFI predicts prognosis in AMI patients treated with PCI. Methods: Patients with newly diagnosed AMI who were treated with PCI at Hunan Provincial People's Hospital from March 2020 to October 2021 were prospectively enrolled. All patients underwent transthoracic echocardiography (TTE) at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. Results: A total of 368 patients with AMI (92 women; mean age, 61.45 ± 11.91 years) were studied with a median follow-up of 14 ± 6.58 months. Sixty-nine patients had endpoint events. Patients who presented with events had a significantly lower LAFI than patients without events (34.25 ± 12.86 vs. 48.38 ± 19.42, P < 0.0001). Multivariate Cox analysis demonstrated that LAFI (HR = 0.97 [95% CI: 0.95; 0.99]; P = 0.012) and the Killip classification (HR = 1.51 [95% CI: 1.03; 2.22]; P = 0.034) were independently predictive of endpoint events. Kaplan-Meier survival curves showed that patients with LAFI ≤ 40.17 cm/ml/m2 had higher events than patients with LAFI > 40.17 cm/ml/m2 (HR = 8.53 [95% CI: 4.74; 15.35]; P < 0.0001). Conclusion: LAFI is a strong and independent predictor of adverse events and can be used for risk stratification in patients with AMI treated with PCI.

Left atrial function index predicts poor outcome in STEMI patients treated with percutaneous coronary intervention.

The prognostic value of the left atrial function index (LAFI) in acute ST segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study sought to determine whether the LAFI predicts prognosis in STEMI patients treated with PCI. Patients with newly diagnosed STEMI who were treated with PCI in Hunan Provincial People's Hospital from March 2020 to October 2020 were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 156 STEMI patients treated with PCI were studied with a median follow-up of 14 months. Forty-eight patients had endpoint events. The LAFI had the highest area under the receiver operating characteristic curve (AUC) predicting the endpoint events, with an AUC of 0.90 (95% CI 0.84-0.94). Multivariate Cox analysis demonstrated that only the LAFI (HR: 0.91, 95% CI 0.87-0.96, P < 0.0001) was independently predictive of endpoint events. Kaplan‒Meier survival curves showed that patients with an LAFI ≤ 42.25 cm/cc/m2 had more events than patients with an LAFI > 42.25 cm/cc/m2 (HR: 19.15, 95% CI 8.90-41.21, P < 0.001). The LAFI is a strong and independent predictor of events in STEMI patients treated with PCI.

SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo, endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis.

Effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome based on 16S rDNA technique. / 基于16S rDNAæŠ€æœ¯æŽ¢è®¨é’ˆç¸å¯¹è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾æ¨¡åž‹å¤§é¼ è‚ é“èŒç¾¤çš„å½±å“.

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS: Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.

[The effect of pitavastatin on blood glucose and its efficacy in diabetic patients with hypercholesterolemia].

OBJECTIVE: To evaluate the effect of pitavastatin on blood glucose in patients with hypercholesterolemia, and to investigate the efficacy of pitavastatin in diabetic patients combined with hypercholesterolemia. METHOD: This study was a 12-week, multi-center, open-label, without parallel-group comparison, phase IV clinical trail. RESULTS: Contrasting to baseline, the prevalences at week 4 and 12 post-treatment of abnormal fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) (FPG: 14.2%vs 14.1% and 11.0%; HbA1c: 14.3% vs 15.1% and 16.1%) in the safety set subjects without diabetes mellitus (DM), as well as in those with DM but not taking glucose-lowering drugs (FPG: 7/7 vs 4/7 and 5/7; HbA1c: 5/5 vs 4/4 and 5/5) had no significant changes (all P values > 0.05). Contrasting to baseline, the levels of TC [(6.51 ± 0.94) mmol/L vs (5.12 ± 0.93) mmol/L and (4.54 ± 1.00) mmol/L], LDL-C [(4.11 ± 0.79) mmol/L vs (3.02 ± 0.81) mmol/L and (2.51 ± 0.70) mmol/L] and TG [2.10 (1.53, 2.54) mmol/L vs 1.62 (1.26, 2.00) mmol/L and 1.35 (1.10, 1.86) mmol/L]at week 4 and 12 post-treatment in the per protocol set 55 subjects with DM were significantly reduced (all P values < 0.05); 33.3% of subjects at high risk and 10.0% of subjects at very high risk had achieved a TC target value; 55.6% of subjects at high risk and 40.0% of subjects at very high risk had achieved a LDL-C target value. CONCLUSION: Pitavastatin has a safe effect on blood glucose and it could be used to treat diabetic patients combined with hypercholesterolemia in China.

[Effect and risk factors of pitavastatin on high sensitivity C-reactive protein in patients with hypercholesterolemia: a multilevel models analysis].

OBJECTIVE: To evaluate the effect of pitavastatin on high sensitivity C-reactive protein (hsCRP) in patients with hypercholesterolemia, and determine risk factors for the effect. METHODS: This study was a 12-week, multicenter, open-label, without parallel-group comparison, phase IV clinical trail. RESULTS: There were 330 subjects in the per protocol set. Contrast to the baseline, the average levels of hsCRP in all of subjects and the group without a history of receiving previous statin medication at week 12 post-treatment decreased respectively 26.4% (1.20 mg/L vs 1.68 mg/L) and 27.5% (1.21 mg/L vs 1.97 mg/L, all P < 0.05). The results of multilevel models indicated that the average levels of hsCRP reduced with the passage of treatment time, the time-varying rate of per-visit was 0.97 mg/L (95% confidence interval 0.96 - 0.98). Controlled individual background covariates, the model predicted that pulse pressure and white blood cell count on the baseline had the significant positive effects on hsCRP (P < 0.01). CONCLUSIONS: Pitavastatin decreases hsCRP in patients with hypercholesterolemia. The main risk factors for the effect are pulse pressure and white blood cell count on the baseline.

[Safety and efficacy of pitavastatin in patients with hypercholesterolemia: a multicenter study].

OBJECTIVE: To evaluate the safety and efficacy of pitavastatin in patients with hypercholesterolemia in China under conditions of extensive usage. METHODS: This was a 12-week, multicenter, open-label, without parallel-group comparison, phase IV clinical trial. RESULTS: There were 427 subjects in the safety set. The adverse events mainly included vomiting, myalgia and the elevations of aspartate transaminase (AST), alanine transaminase (ALT) and creatine kinase (CK), etc. The incidence of drug-related adverse events was 4.22%. There were no significant differences between pre-exposure and post-exposure average levels of renal function indicators and blood routine examination item (all P > 0.05). None of them had a high AST/ALT value, i.e. > 3 times upper limits of normal (ULN), or had a high CK value, i.e. > 10 times ULN. There were 397 subjects in the per protocol set. At week 12 post-treatment, the blood levels of total cholesterol and low density lipoprotein cholesterol (LDL-C) in subjects without previous treatment decreased 24.6% and 31.0% respectively, that of high density lipoprotein cholesterol (HDL-C) in subjects with HDL-C < 1.04 mmol/L increased 60.1% while that of triglyceride (TG) in subjects with TG > 1.70 mmol/L decreased 22.5% (P < 0.05). And 207 (92.3%) subjects were at a low risk, 46 (76.1%) subjects at an intermediate risk, 134 (47.8%) subjects at a high risk and 10 (40.0%) of subjects at a very high risk had achieved a LDL-C target value; the LDL-C goal achievement rate after switching from previous medication to pitavastatin was significant higher than that of pre-switching. CONCLUSION: Pitavastatin demonstrates positive safety and efficacy. It may be used for the treatment of patients with hypercholesterolemia in China.

[Relationship and interactions between elevated fasting glucose and hypertension for cardiocerebral vascular disease].

OBJECTIVE: To explore the relationship and interaction of elevated fasting glucose and hypertension on cardiocerebral vascular disease. METHODS: 10 054 males and females were recruited for our cross-sectional study during May 2007 to August 2007. Unconditional logistic regression was used to analysis the relationship between fasting glucose and hypertension on cardiocerebral vascular disease. A product of fasting glucose and hypertension was added to the logistic regression model to evaluate the multiplicative interaction and relative excess risk of interaction (RERI), attributable proportion (AP) of interaction and synergy index (S) was applied to evaluate the additive interaction of the two factors. Bootstrap was used to calculate 95% confidence intervals (CI) of RERI, AP and S. RESULTS: After adjusting age, gender, smoking, drinking, body mass index (BMI) and region, the product of fasting glucose and hypertension was not statistically significant, which means there was no multiplicative interaction between the two. But the additive indexes RERI, AP and S with 95%CI of diabetes and hypertension were 0.64 (0.03, 1.25), 0.27 (0.01, 0.47) and 1.83 (1.02, 5.13) respectively, which means significant additive interaction was shown between the two on cardiovascular disease but not no stroke. And there were no additive interaction between impaired fasting glucose on cardiovascular disease or stroke. CONCLUSIONS: Hypertension was independently related to cardiovascular disease and stroke in Beijing citizens, and diabetes were independently related to stroke. There was additive interaction between diabetes and hypertension on cardiovascular disease.

Dexmedetomidine Inhibits NF-κB-Transcriptional Activity in Neurons Undergoing Ischemia-Reperfusion by Regulating O-GlcNAcylation of SNW1.

Dexmedetomidine (Dex) is neuroprotective in ischemia-reperfusion (I/R) by suppressing inflammation but the underlying molecular mechanisms are not known. SNW domain-containing protein 1 (SNW1) is a coactivator of the pro-inflammatory transcription factor NF-κB p65. Because SNW1 is regulated by O-GlcNAcylation, we aimed to determine whether this modification influences NF-κB transcriptional activity in neurons undergoing I/R and how Dex may affect the O-GlcNAcylation of SNW1. SH-SY5Y and PC12 cells under hypoxia/reoxygenation (H/R) conditions were treated with Dex and with inhibitors of O-GlcNAc transferase (OGT). O-GlcNAc levels in SNW1 and effects of SNW1 on NF-κB p65 were determined by immunoprecipitation. H/R increased SNW1 protein levels but inhibited O-GlcNAcylation of SNW1. A Luciferase reporter assay demonstrated that increased SNW1 levels led to increased NF-κB p65 activity and increased secretion of neuron-derived inflammatory factors demonstrated by ELISA. Dex reversed the H/R-induced increase of SNW1 protein by upregulating OGT and enhancing O-GlcNAcylation of SNW1. Dex suppression of the SNW1/NF-κB complex resulted in neuroprotection in vitro and in a middle cerebral artery occlusion model in vivo. PKA and ERK1/2 inhibitors abolished the effect of Dex on OGT protein. Taken together, these data indicate that Dex inhibits NF-κB-transcriptional activity in neurons undergoing I/R by regulating O-GlcNAcylation of SNW1.

Risk Factors and Outcome Variables of Cardiorenal Syndrome Type 1 in Acute Myocardial Infarction Patients.

PURPOSE: This study's goal was to explore risk factors affecting short-term prognosis of cardiorenal syndrome type 1 (CRS1) in acute myocardial infarction (AMI) patients. METHODS: In this retrospective analysis of CRS1 in AMI patients hospitalized from January 2011 to December 2014, the patients were classified into deceased or survivor groups. Clinical data, including demographics, laboratory results, and 28-day outcomes, were collected. RESULTS: The incidence rate of CRS1 in AMI patients was 15.2% (274 in 1801). Ultimately, 88 patients were enrolled and 25 (28.4%) were classified into the deceased group, while 63 were classified into the survivor group. There were statistically significant differences between the groups for hypertension, mechanical ventilation, KIDGO stage, NT-proBNP, Hb, ALB, PCI, decreased LVEF, 7th-day SCr value, and the highest SCr value recorded within 7 days (all P < 0.05). Multivariate logistic regression showed that the following factors were significantly related to whether a patient died: requiring mechanical ventilation, increased NT-proBNP levels and 7th-day SCr values, and decreased LVEFs. The APACHE II, SOFA, and SASP II scores on the 7th day were significantly higher in the deceased group (all P < 0.05). The accuracy of APACHE II, SOFA, and SASP II scores on the 7th day for predicting death were 84.1%, 78.4% and 79.5%, respectively. The AUC of 7th-day APACHE II, SOFA, and SASP II scores was 0.844, 0.803, and 0.827, respectively, with no statistically significant differences between the three scores (P > 0.05). CONCLUSION: The mortality rate of CRS1 in AMI patients was 28.4% (25 in 88) within 28 days. Mechanical ventilation, increased NT-proBNP levels, the 7th-day SCr value, and decreased LVEF were related to death in AMI patients with CRS1. APACHE II, SOFA, and SAPS II scores on the 7th day were satisfactorily accurate in predicting death within 28 days.

The Study of Biomechanics and Clinical Anatomy on a Novel Plate Designed for Posterolateral Tibial Plateau Fractures via Anterolateral Approach.

There is no consensus about the optimal internal fixation selection for treatment of posterolateral tibial plateau fracture. This study described a novel plate through an anterolateral approach for posterolateral tibial plateau fractures (PTPFs). We evaluated the biomechanical performance of a novel plate and two conventional internal implants and investigated the anatomic feasibility of the novel plate. The fracture models were randomly assigned into six groups: Groups A-C were the model groups of posterolateral split fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. Groups D-E were the model groups of posterolateral depression fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. We evaluated the biomechanical performance of six model groups by the biomechanical testing and finite element analysis. Progressively increasing axial compressive loads were applied to each synthetic fracture model by using a customized indentor under 250-750 N loads. Meanwhile, we dissected 12 fresh frozen knee specimens and fixed them with the novel plate through the anterolateral approach. We recorded the adjacency of the novel plate to important anatomic structures. Biomechanical testing showed that the novel plate had the least displacement, followed by the posterior buttress plate, and the lateral plate had the most displacement in posterolateral split fracture. There was no significant difference in the displacement between the novel plate and the lateral plate at different loads in posterolateral depression fractures. And the posterior buttress plate showed the most displacement. In the finite element analysis, the maximum stress values of Groups A, B, and C were 383.76, 414.63, and 305.07 MPa under the load of 750 N, respectively. The maximum stress values of Groups D, E, and F were 474.28, 436.31, and 413.4 MPa under the load of 750 N, respectively. In the anatomic study, the placement of the novel plate had a low risk of damage to the important anatomic structures of knee posterolateral corner. The novel plate could be a great choice for the treatment of PTPFs due to better biomechanical performance and easy manipulation.