Risk Factors for New Vertebral Compression Fracture After Percutaneous Vertebral Augmentation: A Retrospective Study.

BACKGROUND Percutaneous vertebral augmentation is the mainstream treatment of osteoporotic vertebral compression fracture (OVCF). New vertebral compression fracture (NVCF) after percutaneous vertebral augmentation may be an issue that cannot be ignored. Nevertheless, the risk factors for NVCF are still uncertain. This research aimed to study the risk factors for NVCF after percutaneous vertebral augmentation. MATERIAL AND METHODS All patients who underwent percutaneous vertebral augmentation for OVCF from January 2019 to December 2020 were enrolled in the study. These patients were divided into NVCF and control groups according to whether they had NVCF. The covariates including sex, age, BMI, diabetes, hypertension, smoking, alcohol, fracture level, surgical method, cement leakage, cement volume, preoperative anterior vertebral height ratio, and Hounsfield unit (HU) value were reviewed. Univariate and multivariate analyses were performed to identify risk factors. RESULTS A total of 279 patients were included in this study, of which 47 had NVCF after percutaneous vertebral augmentation. Univariate analysis demonstrated that there were significant differences in age (OR=1.040, 95% CI=1.003-1.078, P=0.033), BMI (OR=0.844, 95% CI=0.758-0.939, P=0.002) and HU value (OR=0.945, 95% CI=0.929-0.962, P<0.001) between the 2 groups. Multivariate regression analysis revealed that HU value (OR=0.942, 95% CI=0.924-0.960, P<0.001) were independent risk factor for NVCF after percutaneous vertebral augmentation. CONCLUSIONS Hounsfield unit value was an independent risk factor for new vertebral compression fracture after percutaneous vertebral augmentation, whereas age and BMI were not.

Berberine: A Promising Treatment for Neurodegenerative Diseases.

Berberine, as a natural alkaloid compound, is characterized by a diversity of pharmacological effects. In recent years, many researches focused on the role of berberine in central nervous system diseases. Among them, the effect of berberine on neurodegenerative diseases has received widespread attention, for example Alzheimer's disease, Parkinson's disease, Huntington's disease, and so on. Recent evidence suggests that berberine inhibits the production of neuroinflammation, oxidative, and endoplasmic reticulum stress. These effects can further reduce neuron damage and apoptosis. Although the current research has made some progress, its specific mechanism still needs to be further explored. This review provides an overview of berberine in neurodegenerative diseases and its related mechanisms, and also provides new ideas for future research on berberine.

Delayed versus Accelerated Weight-bearing Rehabilitation Protocol Following Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare accelerated and delayed weight-bearing rehabilitation of anterior cruciate ligament reconstruction regarding clinical outcome measures of knee function (International Knee Documentation Committee Subjective Knee Form (IKDC), Lysholm Knee Scoring Scale, Tegner Activity Scale, and Knee Injury and Osteoarthritis Outcome Score (KOOS)), knee laxity, range of movement, quadriceps, and bone tunnel enlargement. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches of Embase, MEDLINE, CINAHL, and the Cochrane Library databases, from inception to February 2021, for studies comparing delayed or accelerated weight-bearing rehabilitation protocol after anterior cruciate ligament reconstruction in adult patients. RESULTS: Nine studies met the eligibility criteria. A meta-analysis revealed a higher risk of knee laxity in the accelerated weight-bearing group. Accelerated weight-bearing may be related to higher IKDC scores, while there was no statistical difference for Lysholm, Tegner, and KOOS scores at a follow-up within 2 years. Four of 5 studies reported no statistical difference for quadriceps strength and range of movement scores, while 2 studies reported bone tunnel enlargement in the accelerated weight-bearing group. CONCLUSION: This systematic review confirmed that accelerated weight-bearing caused more serious knee laxity and bone tunnel widening than delayed weight-bearing after anterior cruciate ligament reconstruction. We therefore recommend that clinicians should select postoperative rehabilitation programmes with caution.

TC2N: A Novel Vital Oncogene or Tumor Suppressor Gene In Cancers.

Several C2 domain-containing proteins play key roles in tumorigenesis, signal transduction, and mediating protein-protein interactions. Tandem C2 domains nuclear protein (TC2N) is a tandem C2 domain-containing protein that is differentially expressed in several types of cancers and is closely associated with tumorigenesis and tumor progression. Notably, TC2N has been identified as an oncogene in lung and gastric cancer but as a tumor suppressor gene in breast cancer. Recently, a large number of tumor-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, and carcinoembryonic antigen, have been identified in a variety of malignant tumors. Differences in the expression levels of TAAs between cancer cells and normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers and as novel targets in cancer treatment. In this review, we summarize the clinical characteristics of TC2N-positive cancers and potential mechanisms of action of TC2N in the occurrence and development of specific cancers. This article provides an exploration of TC2N as a potential target for the diagnosis and treatment of different types of cancers.

Is It Better to Routinely Use Tourniquet for Knee Arthroscopic Surgery: A Systematic Review and Meta-analysis.

The use of tourniquet in knee arthroscopic surgery is a routine technique and provides convenience for the operation. However, the adverse effects caused by tourniquet during the operation are noticed by more and more researchers. The purpose of our study was to perform a systematic review and meta-analysis to assess the effects of tourniquet use in knee arthroscopy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched databases like PubMed, Cochrane library, EMBASE, and Web of Science from inception of the database up to November 20, 2018, using the keywords " anterior cruciate ligament," "meniscectomy," "arthrocopy," etc. to identify randomized clinical trials. A total of 16 randomized controlled trials involving 1,132 participants fulfilled the inclusion criteria with 582 patients in tourniquet group and 550 patients in nontourniquet group. Compared with tourniquet group, nontourniquet group had less postoperative blood loss and less consumption of analgesic. There was no significant difference between the two groups in intraoperatively arthroscopic visualization, postoperative pain score, postoperative quadriceps muscle strength, and operation time. Our study suggested that compared with tourniquet use, arthroscopic surgery of the knee without tourniquet did not appear to have any disadvantage, and the current evidence was more inclined not to use tourniquet as a routine procedure during the knee arthroscopic surgery.

Phage Display Technology and its Applications in Cancer Immunotherapy.

BACKGROUND: Phage display is an effective technology for generation and selection targeting protein for a variety of purpose, which is based on a direct linkage between the displayed protein and the DNA sequence encoding it and utilized in selecting peptides, improving peptides affinity and indicating protein-protein interactions. Phage particles displaying peptide have the potential to apply in the identification of cell-specific targeting molecules, identification of cancer cell surface biomarkers, identification anti-cancer peptide, and the design of peptide-based anticancer therapy. METHOD/RESULTS: Literature searches, reviews and assessments about Phage were performed in this review from PubMed and Medline databases. CONCLUSION: The phage display technology is an inexpensive method for expressing exogenous peptides, generating unique peptides that bind any given target and investigating protein-protein interactions. Due to the powerful ability to insert exogenous gene and display exogenous peptides on the surface, phages may represent a powerful peptide delivery system that can be utilized to develop rapid, efficient, safe and inexpensive cancer therapy methods.

The Role of KLF4 in Alzheimer's Disease.

Krüppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription factors, is widely expressed in range of tissues that play multiple functions. Emerging evidence suggest KLF4's critical regulatory effect on the neurophysiological and neuropathological processes of Alzheimer's disease (AD), indicating that KLF4 might be a potential therapeutic target of neurodegenerative diseases. In this review, we will summarize relevant studies and illuminate the regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon regeneration and iron accumulation to clarify KLF4's status in the pathogenesis of AD.

Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases.

The amygdala is an almond-shaped nucleus located deep and medially within the temporal lobe and is thought to play a crucial role in the regulation of emotional processes. GABAergic neurotransmission inhibits the amygdala and prevents us from generating inappropriate emotional and behavioral responses. Stress may cause the reduction of the GABAergic interneuronal network and the development of neuropsychological diseases. In this review, we summarize the recent evidence investigating the possible mechanisms underlying GABAergic control of the amygdala and its interaction with acute and chronic stress. Taken together, this study may contribute to future progress in finding new approaches to reverse the attenuation of GABAergic neurotransmission induced by stress in the amygdala.

Overexpression of ATP citrate lyase in renal cell carcinoma tissues and its effect on the human renal carcinoma cells in vitro.

ATP citrate lyase (ACLY) is a key enzyme of lipogenesis in cells. However, ACLY expression in renal cell carcinoma (RCC) and its association with clinicopathological parameters remain unclear. The present study aimed to evaluate ACLY expression levels in RCC and adjacent normal tissues. This study included 33 patients with clear cell RCC (ccRCC). ACLY protein was assayed using immunohistochemistry and western blotting methods. ACLY mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction. Serum ACLY concentrations were measured using the ELISA. Compared with adjacent normal tissues, significantly higher levels of ACLY protein expression were observed in all of the ccRCC tissues (P<0.05). ACLY protein levels were positively associated with the T stage and nuclear grade of RCC. ACLY immunostaining was located in the cytoplasm and nucleus. ACLY protein levels and ACC1 mRNA expression in RCC tissues were significantly higher compared with that in adjacent normal tissues (P<0.05). There were no significant differences in serum ACLY concentrations between patients with RCC and health controls (P>0.05). Preliminary evaluation of ACLY function showed that ACLY small interfering RNA downregulation inhibited RCC cell proliferation and migration, but promoted RCC cell apoptosis. ACLY may be a novel biomarker for the evaluation of biological aggressiveness and may be a potential target for RCC treatment.

Berberine produces antidepressant-like effects in ovariectomized mice.

Berberine has been reports to have antidepressant-like effects. However, it is seldom known whether berberine produces antidepressant-like effects in ovariectomized mice, which exhibit depressive-like responses. To examine the antidepressant-like effects of berberine in ovariectomized mice, behavioral tests were conducted, including the forced swimming test and the open field test. To elucidate the mechanisms, levels of BDNF, phosphorylated CREB and phosphorylated eEF2 were analyzed by western blotting, and c-Fos induction was examined by immunohistochemistry. In the forced swimming test, berberine decreased the immobility time in a dose-dependent manner, reversing the depressive-like effect observed in ovariectomized mice, and this effect was blocked by the 5-HT2 antagonist ketanserin. In addition, western blotting indicated that BDNF and peEF2 in the hippocampus, but not pCREB/CREB in the frontal cortex, were affected by berberine treatment. Furthermore, immunohistochemistry demonstrated that the reduction in c-Fos induced by ovariectomy were greater after berberine treatment. Ketanserin also antagonized the effect of berberine on the c-Fos expression. Our findings suggest that berberine exerts antidepressant-like effects in ovariectomized mice, and 5-HT2 receptor activation may be partially related to the antidepressant-like effects of the berberine by BDNF-CREB and eEF2 pathways.

Two-dimensional Penta-BP5 Sheets: High-stability, Strain-tunable Electronic Structure and Excellent Mechanical Properties.

Two-dimensional (2D) crystals exhibit unique and exceptional properties and show promise for various applications. In this work, we systematically studied the structures of a 2D boronphosphide (BP) monolayer with different stoichiometric ratios (BPx, x = 1, 2, 3, 4, 5, 6 and 7) and observed that each compound had a stable 2D structure with metallic or semiconducting electronic properties. Surprisingly, for the BP5 compounds, we discovered a rare penta-graphene-like 2D structure with a tetragonal lattice. This monolayer was a semiconductor with a quasi-direct band gap of 2.68 eV. More importantly, investigation of the strain effect revealed that small uniaxial strain can trigger the band gap of the penta-BP5 monolayer to transition from a quasi-direct to direct band gap, whereas moderate biaxial strain can cause the penta-BP5 to transform from a semiconductor into a metal, indicating the great potential of this material for nanoelectronic device applications based on strain-engineering techniques. The wide and tuneable band gap of monolayer penta-BP5 makes it more advantageous for high-frequency-response optoelectronic materials than the currently popular 2D systems, such as transition metal dichalcogenides and black phosphorus. These unique structural and electronic properties of 2D BP sheets make them promising for many potential applications in future nanodevices.

The effects of herbal medicine on epilepsy.

Traditional herbal medicine plays a significant role in the treatment of epilepsy. Though herbal medicine is widely used in antiepileptic treatment, there is a lack of robust evidence for efficacy and toxicity of most herbs. Besides, the herbal medicine should be subject to evidence-based scrutiny. In this context, we present a review to introduce the effects of herbal medicine on epilepsy. However, hundreds of herbal medicines have been investigated in the available studies. Some commonly used herbal medicines for epilepsy have been listed in our study. The overwhelming majority of these data are based on animal experiments. The lack of clinical data places constraints on the clinical recommendation of herbal medicine. Our study may conduct further studies and provide some insight on the development of anti-epileptic drugs.

In vitro and in vivo evaluation of docetaxel-loaded stearic acid-modified Bletilla striata polysaccharide copolymer micelles.

Bletilla striata polysaccharides (BSPs) have been used in pharmaceutical and biomedical industry, the aim of the present study was to explore a BSPs amphiphilic derivative to overcome its application limit as poorly water-soluble drug carriers due to water-soluble polymers. Stearic acid (SA) was selected as a hydrophobic block to modify B. striata polysaccharides (SA-BSPs). Docetaxel (DTX)-loaded SA-BSPs (DTX-SA-BSPs) copolymer micelles were prepared and characterized. The DTX release percentage in vitro and DTX concentration in vivo was carried out by using high performance liquid chromatography. HepG2 and HeLa cells were subjected to MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazonium bromide) assay to evaluate the cell viability. In vitro evaluation of copolymer micelles showed higher drug encapsulation and loading capacity. The release percentage of DTX from DTX-SA-BSPs copolymer micelles and docetaxel injection was 66.93 ± 1.79% and 97.06 ± 1.56% in 2 days, respectively. The DTX-SA-BSPs copolymer micelles exhibited a sustained release of DTX. A 50% increase in growth inhibition was observed for HepG2 cells treated with DTX-SA-BSPs copolymer micelles as compared to those treated with docetaxel injection for 72 h. DTX-SA-BSPs copolymer micelles presented a similar growth inhibition effect on Hela cells. Furthermore, absolute bioavailability of DTX-SA-BSPs copolymer micelles was shown to be 1.39-fold higher than that of docetaxel injection. Therefore, SA-BSPs copolymer micelles may be used as potential biocompatible polymers for cancer chemotherapy.

The role of 5-HT2c receptor on corticosterone-mediated food intake.

Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice. Both corticosterone and mCPP increased c-Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c-Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5-HT2c receptors and leptin may be involved in the effects of corticosterone-induced hyperphagia.

High-pressure behavior of bromine confined in the one-dimensional channels of zeolite AlPO4-5 single crystals.

We present a joint experimental and theoretical study on the high-pressure behavior of bromine confined in the one-dimensional (1D) nanochannels of zeolite AlPO4-5 (AFI) single crystals. Raman scattering experiments indicate that loading bromine into AFI single crystals can lead to the formation of bromine molecular chains inside the nanochannels of the crystals. High-pressure Raman and X-ray diffraction studies demonstrate that high pressure can increase the length of the confined bromine molecular chains and modify the inter- and intramolecular interactions of the molecules. The confined bromine shows a considerably different high-pressure behavior to that of bulk bromine. The pressure-elongated bromine molecular chains can be preserved when the pressure is reduced to ambient pressure. Theoretical simulations explain the experimental results obtained from the Raman spectroscopy and X-ray diffraction studies. Furthermore, we find that the intermolecular distance between confined bromine molecules gradually becomes comparable to the intramolecular bond length in bromine molecules upon compression. This may result in the dissociation of the bromine molecules and the formation of 1D bromine atomic chains at pressures above 24 GPa. Our study suggests that the unique nanoconfinement has a considerable effect on the high-pressure behavior of bromine, and the confined bromine species concomitantly enhance the structural stability of the host AFI single crystals.

The survivin suppressant YM155 reverses doxorubicin resistance in osteosarcoma.

Doxorubicin (DOX) is one of the widely used chemotherapeutic drugs for the treatment of human osteosarcoma (OS). However, acquisition of DOX resistance is common in patients with OS, leading to local and distant failure. In this study, we demonstrate that survivin expression is significantly upregulated in OS primary tumors compared to paired normal tissue. In addition, survivin expression was further increased in DOX resistant cells (MG63/DOX) as compared to its parent cells (MG63). Thus, we hypothesize that targeting of survivin in OS could reverse the DOX resistant phenotype in tumor cells thereby enhancing the therapeutic efficacy of DOX. We test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with DOX in vitro and in vivo. We found that combination treatment of YM155 and DOX in DOX resistant cells (MG63/DOX) could significantly inhibited cell proliferation and colony formation, induce cell apoptosis and promoted caspase-3, -8, and -9 activity in vitro, and promoted tumor regression in established OS xenograft models. Taken together, the evidence presented here supports the favorable preclinical evaluation that YM155 could overcome DOX the resistance in tumor cells thereby enhancing the effectiveness of DOX in OS, suggesting that YM155 in combination with DOX has potential in the treatment of osteosarcoma.

The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice.

Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.

Additive antidepressant-like effects of fasting with imipramine via modulation of 5-HT2 receptors in the mice.

Recently, studies show that intermittent fasting and caloric restriction may improve symptoms of depression. However, there is little scientific evidence regarding the literature on the antidepressant-like effects of acute fasting. The present study aims to investigate the antidepressant-like effects and its influence on brain levels of the transcription factor cAMP response element-binding protein (CREB) and its phosphorylated form (p-CREB) in different time periods of fasting mice. Furthermore, the additive antidepressant-like effects of fasting with imipramine and the possible involvement of the 5-HT2 receptors were examined. In the present study 9h, but not 3h and 18h of fasting significantly reduced immobility time in the forced swimming test (FST) without alteration in locomotor activity in the open field test. 9h fasting also enhanced the ratio of p-CREB/CREB in the frontal cortex and hippocampus. Co-administration of 9h of fasting and imipramine (30mg/kg, i.p) produced the additive antidepressant-like effects in the FST and increased the ratio of p-CREB/CREB. Meanwhile, the additive effects were partially reversed by treatment with a 5-HT2A/2C receptor agonist, (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) (5mg/kg, s.c). Furthermore, the antidepressant-like effects of 9h fasting was also blocked by DOI compared to the non-fasting control group. Serum corticosterone level, but not 5-HT and noradrenaline, was significantly increased in a time-dependent manner following different time periods of fasting. Taken together, these results suggest that acute fasting produces antidepressant-like effects via enhancement of the p-CREB/CREB ratio, and additive antidepressant-like effects of fasting with imipramine may be related to modulating 5-HT2 receptors.