Stiffness changes in internal rotation muscles of the shoulder and its influence on hemiplegic shoulder pain.

Background: Hemiplegic shoulder pain (HSP) is a common complication in patients with stroke. The pathogenesis of HSP is complex, and muscle hypertonia, especially the hypertonia of internal rotation muscles of the shoulder, may be one of the important causes of shoulder pain. However, the relationship between muscle stiffness and HSP has not been well studied. The purpose of this study is to explore the correlations between the stiffness of internal rotation muscles and clinical symptoms in patients with HSP. Methods: A total of 20 HSP patients and 20 healthy controls were recruited for this study. The stiffness of internal rotation muscles was quantified using shear wave elastography, and Young's modulus (YM) of the pectoralis major (PM), anterior deltoid (AD), teres major ™, and latissimus dorsi (LD) were measured. Muscle hypertonia and pain intensity were evaluated using the Modified Ashworth Scale (MAS) and Visual Analog Scale (VAS), respectively. The mobility of the shoulder was evaluated using the Neer score. The correlations between muscle stiffness and the clinical scales were analyzed. Results: YM of internal rotation muscles on the paretic side was higher than that of the control group in the resting and passive stretching positions (P < 0.05). YM of internal rotation muscles on the paretic side during passive stretching was significantly higher than that at rest (P < 0.05). YM of PM, TM, and LD during passive stretching were correlated with MAS (P < 0.05). In addition, the YM of TM during passive stretching was positively correlated with VAS and negatively correlated with the Neer score (P < 0.05). Conclusion: Increased stiffness of PM, TM, and LD was observed in patients with HSP. The stiffness of TM was associated with pain intensity of the shoulder and shoulder mobility.

Association of lung-intestinal microecology and lung cancer therapy.

In recent years, the incidence of lung cancer is increasing. Lung cancer has become one of the most malignant tumors with the highest incidence in the world, which seriously affects people's health. The most important cause of death of lung cancer is metastasis. Therefore, it is crucial to understand the mechanism of lung cancer progression and metastasis. This review article discusses the physiological functions, pathological states and disorders of the lung and intestine based on the concepts of traditional Chinese medicine (TCM), and analyzes the etiology and mechanisms of lung cancer formation from the perspective of TCM. From the theory of "the exterior and interior of the lung and gastrointestinal tract", the theory of "the lung-intestinal axis" and the progression and metastasis of lung cancer, we proposed e "lung-gut co-treatment" therapy for lung cancer. This study provides ideas for studying the mechanism of lung cancer and the comprehensive alternative treatment for lung cancer patients.

Contribution of AMPA Receptor-Mediated LTD in LA/BLA-CeA Pathway to Comorbid Aversive and Depressive Symptoms in Neuropathic Pain.

Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.SIGNIFICANCE STATEMENT Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPAR endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.

Mixed Reality Combined with Three-Dimensional Printing Technology in Total Hip Arthroplasty: An Updated Review with a Preliminary Case Presentation.

Three-dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59-year-old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head-mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real-time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.

[Effects of Notch signal on the expressions of HIF-α and autophagy- related genes Beclin1, LC3I, LC3II in oxygen-glucose deprivation induced myocardial cell injury].

OBJECTIVE: To investigate the effects of Notch signal on hypoxic induction factor (HIF-1α) and autophagy-associated genes Beclin1, LC3I, LC3II in oxygen-glucose deprivation (OGD) induced myocardial cell injury. METHODS: The OGD model was established using hypoxic culture box and hypoglycemic DMEM medium. The cells were divided into normal control group, OGD group, OGD + NC siRNA group, OGD + Notch1 siRNA group and OGD + HIF-1α siRNA group. Western blot was used to detect the interference effects of HIF-1α siRNA and Notch1 siRNA. The effects of Notch1 siRNA and HIF-1α siRNA on the activity of myocardial cells in OGD model were detected by the CCK-8 assay. The effects of Notch1 siRNA and HIF-1α siRNA on autophage-associated genes Beclin1, LC3I and LC3II expression were detected by Western blot. RESULTS: The results of Western blot showed that HIF-1α siRNA could effectively knock down the expression of HIF-1α in myocardial cells in OGD model, and Notch1 siRNA could effectively knock down the expression of Notch1 and HIF-1α in myocardial cells in OGD model. The result of CCK-8 assay showed that Notch1 siRNA and HIF-1α siRNA reduced the activity of myocardial cells in OGD model, and there was no statistical difference between the two groups. Western blot results showed that Notch1 siRNA and HIF-1α siRNA could reduce the expressions of the autophagy-associated genes Beclin1, LC3I and LC3II, and reduce the ratio of LC3II to LC3I at mRNA level. CONCLUSION: Notch1 plays a role in myocardial protection by regulating the expression of HIF-1α to regulate the autophagy in OGD model cells.

In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/ß-catenin signaling pathway.

This study aims to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/ß-catenin signaling pathway. BC and normal breast tissues were obtained from 396 female BC patients and 308 female patients with benign breast lesions respectively. Human normal mammary epithelial (MCF-10A) and BC cell lines (BT-20, MCF-7, T-47D and MDA-MB-231) were cultured. After cell transfection, BC cells were assigned to six groups: control, miR-27a mimics, miR-27a inhibitors, negative control (NC), si-SFRP1 and si-SFRP1 + miR-27a inhibitors groups. qRT-PCR assay and Western blot were employed to detect the expressions of miR-27a, SFRP1, Wnt, ß-catenin and GSK3ß. MTT assay, wound-healing test and Transwell assay were used to test cell proliferation, migration and invasion. BC tissues were found to have higher miR-27a expression and lower SFRP1 mRNA and protein expressions than MCF-10A cells and normal breast tissues. Compared with the control and NC groups, the miR-27a mimics and si-SFRP1 groups exhibited down-regulation of SFRP1, up-regulation of Wnt, ß-catenin and GSK3ß, and promotion of cell proliferation, migration and invasion. The miR-27a inhibitor group showed up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the miR-27a mimic group. The si-SFRP1 + miR-27a inhibitors group also exhibited up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the si-SFRP1 group. miR-27a may activate the Wnt/ß-catenin signaling pathway by negatively regulating SFRP1 to promote the proliferation, migration and invasion of BC cells.

Adenotonsillectomy outcomes regarding bone age and osteocalcin in treatment of obstructive sleep apnea syndrome in children.

BACKGROUND: To investigate the effect of adenotonsillectomy (AT) on bone development, quality of life and polysomnography evaluation in children with obstructive sleep apnea syndrome (OSA). METHODS: Preoperative and postoperative (6 months) physical examination, PSG, bone age (BA) and osteocalcin (OC) evaluation were performed on the selected OSA children (n=92) and the healthy children (n=87). The OSA children were also scored based on the OSA 18-item questionnaire. A two-year follow-up was conducted to evaluate BA and OC changes. RESULTS: After AT, 81 (88.04%) OSA children recovered completely, eight (8.70%) achieved remarkable improvements, and three (3.26%) achieved moderate improvements. In the OSA children, postoperative OSA 18-item score and the scores of the five domains were significantly higher than preoperative ones. Compared with the preoperative, body mass index (BMI), weight for age Z-sores, height for age Z-sores, weight for height Z-sores and BMI Z-score in the OSA group 6 months after the operation were significantly increased, but no significant difference was detected between the OSA and the control group. The changes of BA and chronological age in the OSA group were significantly different from those in the control group. Two years after AT, BA between the two groups was no longer significantly different. Preoperative serum OC in the OSA group was lower than that in the control group, but increased to normal levels 6 months after AT. Correlation analysis showed serum OC levels were negatively correlated with apnea hyponea index, obstructive apnea index, arousal index, and lowest oxygen saturation. CONCLUSIONS: After AT, bone growth and development in children with OSA recovered gradually, and the serum OC levels decreased to the normal level. Therefore, preventive measures and positive treatments should be applied to minimize the negative effects of OSA in children.

Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in the development of bone cancer pain in a rat model.

Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the pathogenesis of bone cancer pain still remain largely unknown. Previously, we have reported that sensitization of primary sensory dorsal root ganglion (DRG) neurons contributes to the pathogenesis of bone cancer pain in rats. In addition, numerous preclinical and clinical studies have revealed the pathological roles of interleukin-6 (IL-6) in inflammatory and neuropathic hyperalgesia. In this study, we investigated the role and the underlying mechanisms of IL-6 in the development of bone cancer pain using in vitro and in vivo approaches. We first demonstrated that elevated IL-6 in DRG neurons plays a vital role in the development of nociceptor sensitization and bone cancer-induced pain in a rat model through IL-6/soluble IL-6 receptor (sIL-6R) trans-signaling. Moreover, we revealed that functional upregulation of transient receptor potential vanilloid channel type 1 (TRPV1) in DRG neurons through the activation of Janus kinase (JAK)/phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to the effects of IL-6 on the pathogenesis of bone cancer pain. Therefore, suppression of functional upregulation of TRPV1 in DRG neurons by the inhibition of JAK/PI3K pathway, either before surgery or after surgery, reduces the hyperexcitability of DRG neurons and pain hyperalgesia in bone cancer rats. We here disclose a novel intracellular pathway, the IL-6/JAK/PI3K/TRPV1 signaling cascade, which may underlie the development of peripheral sensitization and bone cancer-induced pain.

In vivo ossification of a scaffold combining ß-tricalcium phosphate and platelet-rich plasma.

Tricalcium phosphate (TCP) and platelet-rich plasma (PRP) are commonly used in bone tissue engineering. The aim of the present study was to investigate a composite that combined TCP with PRP and assess its effectiveness in the treatment of bone defects. Cavity-shaped bone defects were established on the tibiae of 27 beagle dogs, and were repaired by pure ß-TCP with bone marrow stromal cells (BMSCs), ß-TCP/PRP with BMSCs and autogenic ilium. The samples were harvested at 4, 8 and 12 weeks, and bone regeneration was evaluated using X-ray radiography, immunocytochemical staining of osteocalcin (OCN), hematoxylin and eosin staining and reverse transcription-polymerase chain reaction analyses. Biomechanical tests of the scaffolds were performed at the 12th week after scaffold implantation. When using pure ß-TCP as a scaffold, the scaffold-bone interface was clear and no material adsorption and bone healing was observed. Substantial bone regeneration was observed when the tibial defects were restored using ß-TCP/PRP and autogenic ilium. Furthermore, the mRNA expression levels of OCN, alkaline phosphatase and collagen type I α1 were significantly higher in the animals with ß-TCP/PRP scaffolds at 8 and 12 weeks following implantation compared with those in the animals with the pure ß-TCP scaffolds. The maximum load and compressive strength of the ß-TCP/PRP scaffolds were similar to those of the autogenic ilium; however, they were significantly higher than those of the pure ß-TCP scaffold. Thus, the ß-TCP/PRP composite may be used as a potential scaffold to carry in vitro cultured BMSCs to treat bone defects.

Sensitization of neurons in the central nucleus of the amygdala via the decreased GABAergic inhibition contributes to the development of neuropathic pain-related anxiety-like behaviors in rats.

BACKGROUND: Despite high prevalence of anxiety accompanying with chronic pain, the mechanisms underlying pain-related anxiety are largely unknown. With its well-documented role in pain and emotion processing, the amygdala may act as a key player in pathogenesis of neuropathic pain-related anxiety. Pain-related plasticity and sensitization of CeA (central nucleus of the amygdala) neurons have been shown in several models of chronic pain. In addition, firing pattern of neurons with spike output can powerfully affect functional output of the brain nucleus, and GABAergic neurons are crucial in the modulation of neuronal excitability. In this study, we first investigated whether pain-related plasticity (e.g. alteration of neuronal firing patterns) and sensitization of CeA neurons contribute to nerve injury-evoked anxiety in neuropathic rats. Furthermore, we explored whether GABAergic disinhibition is responsible for regulating firing patterns and intrinsic excitabilities of CeA neurons as well as for pain-related anxiety in neuropathic rats. RESULTS: We discovered that spinal nerve ligation (SNL) produced neuropathic pain-related anxiety-like behaviors in rats, which could be specifically inhibited by intra-CeA administration of anti-anxiety drug diazepam. Moreover, we found potentiated plasticity and sensitization of CeA neurons in SNL-induced anxiety rats, of which including: 1) increased burst firing pattern and early-adapting firing pattern; 2) increased spike frequency and intrinsic excitability; 3) increased amplitude of both after-depolarized-potential (ADP) and sub-threshold membrane potential oscillation. In addition, we observed a remarkable reduction of GABAergic inhibition in CeA neurons in SNL-induced anxiety rats, which was proved to be important for altered firing patterns and hyperexcitability of CeA neurons, thereby greatly contributing to the development of neuropathic pain-related anxiety. Accordantly, activation of GABAergic inhibition by intra-CeA administration of muscimol, a selective GABAA receptors agonist, could inhibit SNL-induced anxiety-like behaviors in neuropathic rats. By contrast, suppression of GABAergic inhibition by intra-CeA administration of bicuculline, a selective GABAA receptors antagonist, produced anxiety-like behavior in normal rats. CONCLUSIONS: This study suggests that reduction of GABAergic inhibition may be responsible for potentiated plasticity and sensitization of CeA neurons, which likely underlie the enhanced output of amygdala and neuropathic pain-related anxiety in SNL rats.

Absence of gamma-interferon-inducible lysosomal thiol reductase (GILT) is associated with poor disease-free survival in breast cancer patients.

Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P<0.001). In accordance with its proliferation inhibiting function, GILT expression was inversely correlated with Ki67 index (P<0.05). In addition, absence of GILT was positively correlated with adverse characteristics of breast cancers, such as histological type, tumor size, lymph nodes status, and pTNM stage (P<0.05). Consistently, breast cancers with reduced GILT expression had poorer disease-free survival (P<0.005). Moreover, significantly decreased expression of GILT was found in both primary and metastatic breast cancer cells, in contrast to normal epithelial cells. These findings indicate that GILT may act as a tumor suppressor in breast cancer, in line with its previously suggested role in anti-tumor immunity. Thus, GILT has the potential to be a novel independent prognostic factor in breast cancer and further studies are needed to illustrate the underlying mechanism of this relationship.

Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication.

This study aimed to identify gene expression profile in the rat brain resulting from acute alcohol intoxication (AAI). Eighteen SD rats were divided into the alcohol-treated group (n = 9) and saline control group (n = 9). Periorbital blood samples were taken to determine their blood alcohol content by gas chromatography. Tissue sections were analyzed by H and E staining and biochemical assays. Real-time reverse transcription PCR was used to validate microarray data. Statistical analysis was carried out using SPSS18.0 software (Version 18.0, SPSS Inc., Chicago, IL, USA). H and E staining demonstrated that alcohol-treated rats showed no obvious pathological changes in nerve cells compared with those in the control group. Biochemical tests revealed that alcohol-treated rats had lower superoxide dismutase activity than those in the control group (167.3 ± 10.3 U/mg vs. 189.2 ± 5.9 U/mg, P < 0.05). Furthermore, the malondialdehyde levels in alcohol-treated rats were higher than those in the control group (3.48 ± 0.24 mmol/mg vs. 2.51 ± 0.23 mmol/mg, P < 0.05). Microarray data presented 366 up-regulated genes and 300 down-regulated genes in the AAI rat brain. Gene ontology analysis identified 31 genes up-regulated and 39 down-regulated among all differentially expressed genes. Twenty-four pathways showed significant differences, including 12 pathways involved with up-regulated genes and 12 pathways involved with down-regulated genes. Selected genes showed significantly different expression in both alcohol-treated and control groups (P < 0.05). Gene expression analysis enabled clustering of alcohol intoxication-related genes by function. These genes expression may be potential targets for treatment or drug screening for acute alcohol intoxication.

Serum Brain-derived neurotrophic factor levels in Chinese children with autism spectrum disorders: a pilot study.

Brain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of Autism spectrum disorders (ASD). The purpose of this study was to investigate the potential role of BDNF in Chinese children with ASD. Sixty patients (48 male, 12 female) diagnosed with ASD and 60 healthy sex and age control subjects were assessed for serum BDNF content at admission. BDNF were assayed with enzyme-linked immunosorbent assay methods, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. The results indicated that the median serum BDNF levels were significantly (P<0.0001) higher in children with ASD as compared to normal cases [17.6(IQR: 13.7-21.4) ng/ml and 11.5(9.6-13.8) ng/ml, respectively]. Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value of serum BDNF levels as an indicator for auxiliary diagnosis of autism was projected to be 15.0 ng/ml. Further, we found that an increased risk of ASD was associated with BDNF levels >15.0 ng/ml (adjusted OR 10.4, 95% CI: 4.39-29.32) after adjusting for above possible confounders. Our study demonstrated that serum BDNF levels were associated with ASD, and higher levels could be considered as an independent risk factor of ASD.

[Removal of organic pollutants by adsorption cooperated with biodegradation in BAC].

The determination measure for distribution of NOM removal by two mechanisms in BAC was established. In this method, the change in DOC and BDOC of inflow and effluent was used to evaluate the distribution and to determinate the effect of the different ozone doses on the adsorption and biodegradation in BAC. The ozonation increased the concentration of BDOC in 0.12 - 0.54 mg/L with ozone dose of 2 - 8 mg/L and BAC filtration decreased concentration of BDOC to 0.23 - 0.31 mg/L. Moreover the biodegradation distribution to remove the organic pollutants increased from 46% to 89% with ozone dose of 2 - 8 mg/L.

[Determination for optimal ozone dose in O3-BAC].

The ozonation can increase biodegradability of water and the biofilter after ozonation can increase biostability of water. The result shows that with different doses of ozone between 2 and 8 mg/L, ozonation can increase AOC-P17, AOC-NOX and BDOC by 20.9%-85.5%, 42.1%-158.2% and 21.4%-84.4%, respectively. The optimum ozone dose for maximum AOC and BDOC formation is 3 mg/L. In the test, the AOC of effluent from BAC is lower than 50 microg/L (acetate-C). The AOC concentration is between 35.9 and 46.6 microg/L (acetate-C), and the effluent belongs to biostability.

[Study on prevalence and correlation factors of bronchial asthma in Zaozhuang area, Shandong province].

OBJECTIVE: To study the prevalence of asthma and its correlated factors in Zaozhuang area in 2003, to provide a basic consideration for prevention/treatment and control policy. METHODS: 6 points were selected by stratified-clusterd-random sampling with a total of 16,725 persons expected, but only 10,610 subjects investigated. RESULTS: In this survey, 128 asthma cases were identified with a overall prevalence of 1.21%. The prevalence for children was 2.02%, and for adult was 0.90% with the former significantly higher then the latter (chi(2) = 21.39, P < 0.01). Rates for male and female were 1.08%, 1.32% with a ratio of 1:1.22. For 77.97% of children with asthma. The initiative age of asthma was before 7 years old among children while among 36.23% of the adults, it was before 15 years of age. Correlation analysis showed that upper respiratory tract infection (OR = 17.81, 95% CI: 12.25-25.89), cold air exposure (OR = 3.43, 95% CI: 2.41-4.90), stimulation through cooking and by harmful gases (OR = 2.56, 95% CI: 1.80-3.63), allergic materials (OR = 2.74, 95% CI: 1.80-4.17) were main inducing factors. 65.63% of the asthma cases having had history of allergic disease while 25.78% having had family history with the OR of allergic history and family history as 21.69 vs. 73.96. CONCLUSION: The epidemic status of bronchial asthma was serious, with an assumption that asthma cases might have reached the number of 43 thousand in Zaozhuang area.