What is the impact of knee morphology on posterior cruciate ligament avulsion fracture in men and women: a case control study.

BACKGROUND: Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture. METHODS: 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture. RESULTS: Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05). CONCLUSIONS: Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.

Is acupuncture a placebo therapy?

Complementary therapies such as acupuncture are suggested to have enhanced placebo effects. Numerous high quality randomized controlled trials found that acupuncture is no better than its placebo control; however, patients in both real and sham acupuncture groups report clinically meaningful symptom improvements. A possible interpretation of these trials is that acupuncture acts entirely by engaging placebo mechanisms. This article provides further evidence supporting that acupuncture might be a potent placebo, and explains how to address major concerns following this suggestion.

The D1 dopamine receptor agonist, SKF83959, attenuates hydrogen peroxide-induced injury in RGC-5 cells involving the extracellular signal-regulated kinase/p38 pathways.

PURPOSE: Oxidative stress is widely implicated in the death of retinal ganglion cells associated with various optic neuropathies. Agonists of the dopamine D(1) receptor have recently been found to be potentially neuroprotective against oxidative stress-induced injury. The goal of this study was to investigate whether SKF83959, a next-generation high-affinity D(1) receptor agonist, could protect retinal ganglion cell 5 (RGC-5) cells from H(2)O(2)-induced damage and the molecular mechanism involved. METHODS: We examined expression of the D(1) receptor in RGC-5 cells with reverse-transcription-PCR and immunoblotting and assessed neuroprotection using propidium iodide staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, we monitored the activation and involvement of members of mitogen-activated protein kinase family, extracellular signal-regulated kinase (ERK), p38 and c-Jun NH(2)-terminal kinase, with western blot and specific inhibitors. RESULTS: We found that the D(1) receptor was expressed in RGC-5 cells, but the sequence analysis suggested this cell line is from mouse and not rat origin. SKF83959 exhibited a remarkable neuroprotective effect on H(2)O(2)-damaged RGC-5 cells, which was blocked by the specific D(1) receptor antagonist, SCH23390. ERK and p38 were activated by SKF83959, and pretreatment with their inhibitors U0126 and SB203580, respectively, significantly blunted the SKF83959-induced cytoprotection. However, the specific c-Jun NH(2)-terminal kinase inhibitor, SP600125, had no effect on the SKF83959-induced protection. CONCLUSIONS: We conclude that SKF83959 attenuates hydrogen peroxide-induced injury in RGC-5 cells via a mechanism involving activation of the ERK and p38 pathways and the D(1) receptor is a potential molecular target for developing neuroprotective drugs.

Calcium overload is a critical step in programmed necrosis of ARPE-19 cells induced by high-concentration H2O2.

OBJECTIVE: Oxidative stress plays an important role in retinal pigmental epithelium (RPE) death during aging and the development of age-related macular degeneration. Although early reports indicate that reactive oxygen species (ROS) including H2O2 can trigger apoptosis at lower concentrations and necrosis at higher concentrations, the exact molecular mechanism of RPE death is still unclear. The purpose of this study was to investigate the molecular pathways involved in RPE death induced by exogenous ROS, especially at higher concentrations. METHODS: Cultured ARPE-19 cells were treated with H2O2 at different concentrations and cell viability was measured with the MTT assay. Cell death was morphologically studied by microscopy using APOPercentage assay and PI staining. Furthermore, the impact of oxidative stress on ARPE-19 cells was assessed by HO-1 and PARP-1 Western blotting and by the protection of antioxidant EGCG. Calcium influx was determined using the fura-2 calcium indicator and the role of intracellular calcium overload in ARPE-19 cell death was evaluated following cobalt treatment to block calcium effects. RESULTS: H2O2 reduced the viability of ARPE-19 cells in a concentration-dependent manner, which was presented as a typical s-shaped curve. Cell death caused by high concentrations of H2O2 was confirmed to be programmed necrosis. Morphologically, dying ARPE-19 cells were extremely swollen and lost the integrity of their plasma membrane, positively detected with APOPercentage assay and PI staining. 24-hour treatment with 500 µmol/L H2O2 induced remarkable up-regulation of HO-1 and PARP-1 in ARPE-19 cells. Moreover, antioxidant treatment using EGCG effectively protected cells from H2O2-induced injury, increasing cell viability from 14.17%±2.31% to 85.77%±4.58%. After H2O2 treatment, intracellular calcium levels were highly elevated with a maximum concentration of 1200 nM. Significantly, the calcium channel inhibitor cobalt was able to blunt this calcium influx and blocked the necrotic pathway, rescuing the ARPE-19 cell from H2O2-induced death. CONCLUSIONS: At high concentrations, H2O2 induces ARPE-19 cell death through a regulated necrotic pathway with calcium overload as a critical step in the cell death program.

Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene.

AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells that were wild type for PTEN. METHODS: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells. The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo. RESULTS: Adenovirus-mediated transfer of PTEN (Ad-PTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901) carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore, treatment of human gastric tumor xenografts (MGC-803, SGC-7901) with Ad-PTEN resulted in a significant (P<0.01) suppression of tumor growth. CONCLUSION: These results indicate a significant tumor-suppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.

[The expression of connective tissue growth factor in renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin].

OBJECTIVE: To investigate the connective tissue growth factor (CTGF) mRNA expression in the renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. METHODS: Twenty-four rats underwent operation 2 times: during the first operation 2/3 of the left kidney was resected, and the right kidney was resected completely one week after. The 24 5/6 nephrectomized rats were randomly divided into 2 groups: untreated 5/6 nephrectomized group (model group, n=12) and fluvastatin-treated 5/6 nephrectomized group (treatment group, fluvastatin was orally administered 7 mg.kg(-1).d(-1) for 13 weeks, n=12), and 6 sham-operated rats served as control (sham operation group). In the weeks 2, 4, 8, and 13 after the second operation metabolic cage was used to collect the 24-hour urine 2 times. Urine protein was examined by biuret reaction so as to calculate urinary protein excretion. By the end of experiment blood was collected to examine the serum cholesterol, triglyceride, urea nitrogen, and creatinine contents. The rats were killed and their kidneys taken out. The CTGF mRNA expression in the renal cortex was detected by RT-PCR. Immunohistochemistry was used to examine the expression of transforming growth factor-beta1 (TGF-beta1), type IV collagen and fibronectin in the glomeruli. Renal pathological changes and glomerular sclerosis index (GSI) were evaluated as well. RESULTS: At the end of the experiment, the mean urinary protein excretion in the model group was 305.4 mg/24 h, significantly higher than that in the treatment group (230.9 mg/24 h, P<0.01) and the sham operation group (5.6 mg/24 h, P<0.01) The serum urea nitrogen of the model group was (24.5 +/- 4.9) mmol/L, significantly higher than that of the treatment group [(15.8 +/- 3.9) mmol/L, P<0.05] and that of the sham-operated group (7.4 +/- 0.3 mmol/L, P<0.01). The serum creatinine (P<0.05) of the model group was 88 micromol/L +/- 14 micromol/L, significantly higher than that of the treatment group [(58 +/- 5) micromol/L, P<0.05)] and that of the sham-operated group [(54 +/- 5) micromol/L, P<0.05]. The creatinine clearance rate of the model group was (1.7 +/- 0.7) ml.min(-1).kg(-1), significantly lower than that of the treated group [(3.2 +/- 1.1) ml.min(-1).kg(-1), P<0.05] and that of the sham-operated group [(3.9 +/- 1.5) ml.min(-1).kg(-1), P<0.05]. The glomerular sclerosis index (GSI) in the model group was 41.8 +/- 11.5, significantly higher than that in the sham operation group (2.2 +/- 1.3, P<0.01) and the treatment group (23.4 +/- 6.1, P<0.05). The mean optical density of CTGF mRNA expression in the renal cortex of the model group was a 3 times that of the sham operation group, and the mean optical density of CTGF mRNA expression in the renal cortex of the treatment group was lower by 55.4% compared with that of the model group (P<0.01). The glomerular expressions of TGF-beta1, type IV collagen and fibronectin were significantly up-regulated in the model group in comparison with those in the sham operation group (all P<0.01). The glomerular protein expressions of TGF-beta1, type IV collagen and fibronectin were significantly weaker in the fluvastatin treatment group as compared with the model group (all P<0.01). CONCLUSION: CTGF mRNA expression is markedly upregulated in the renal cortex of 5/6 nephrectomized rats. Fluvastatin suppresses the increased CTGF mRNA expression in renal cortex and ameliorates the glomerular extracellular matrix accumulation.