Third Hospital of Hebei Medical University

Age-associated memory impairment (AAMI) occurs in many mammalian species, including humans. In contrast to Alzheimer's disease (AD), in which circuit disruption occurs through neuron death, AAMI is due to circuit and synapse disruption in the absence of significant neuron loss and thus may be more amenable to prevention or treatment. We have investigated the effects of aging on pyramidal neurons and synapse density in layer III of area 46 in dorsolateral prefrontal cortex of young and aged, male and female rhesus monkeys (Macaca mulatta) that were tested for cognitive status through the delayed non-matching-to-sample (DNMS) and delayed response tasks. Cognitive tests revealed an age-related decrement in both acquisition and performance on DNMS. Our morphometric analyses revealed both an age-related loss of spines (33%, p < 0.05) on pyramidal cells and decreased density of axospinous synapses (32%, p < 0.01) in layer III of area 46. In addition, there was an age-related shift in the distribution of spine types reflecting a selective vulnerability of small, thin spines, thought to be particularly plastic and linked to learning. While both synapse density and the overall spine size average of an animal were predictive of number of trials required for acquisition of DNMS (i.e., learning the task), the strongest correlate of behavior was found to be the head volume of thin spines, with no correlation between behavior and mushroom spine size or density. No synaptic index correlated with memory performance once the task was learned.

PURPOSE: To investigate whether exposure of human corneal epithelial cells to hyperosmotic stress activates the c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway, and stimulates production of the matrix metalloproteinases (MMPs): gelatinase (MMP-9), collagenases (MMP-1 and -13), and stromelysin (MMP-3). METHODS: Primary human corneal epithelial cells cultured in normal osmolar medium (312 mOsM) were exposed to media with higher osmolarity (350-500 mOsM) achieved by adding NaCl, with or without SB202190, an inhibitor of the JNK pathway; dexamethasone; or doxycycline for different lengths of time. The conditioned media were collected after 24 hours of exposure for zymography and ELISA. Total RNA was extracted from cultures treated for 6 hours and subjected to semiquantitative RT-PCR. Cells treated for 5 to 60 minutes were lysed in RIPA buffer and subjected to Western blot with phospho (p)-specific antibodies against p-JNK and p-c-Jun. JNK1 activation was also detected with an immunoassay system. RESULTS: The concentrations of MMP-9, -1, and -3 proteins in 24-hour conditioned media of corneal epithelial cells progressively increased as the media's osmolarity was increased from 312 to 500 mOsM by the addition of NaCl. The concentration of MMP-13 progressively increased to a peak at 450 mOsM. Active p-JNK-1, p-JNK-2, and p-c-Jun were detected by Western blot as early as 5 minutes and peaked at 60 minutes in cells exposed to hyperosmolar media. The levels of p-JNK-1, p-JNK-2, and p-c-Jun correlated positively with the osmolarity of the culture media. The p-JNK inhibitor SB202190 and doxycycline markedly inhibited the stimulation of p-JNK-1, p-JNK-2, and p-c-Jun, as well as MMP-9, -1, -13, and -3 at both the mRNA and protein levels in the cells exposed to hyperosmolar media. CONCLUSIONS: Expression and production of MMP-9, -1, -13, and -3 by human corneal epithelial cells correlated positively with increasing media osmolarity. This increase was mediated at least in part through activation of the JNK SAPK pathway. Doxycycline, an agent used to treat MMP-mediated ocular surface disease, inhibited the hyperosmolarity-induced MMP production and JNK activation. The relevance of these findings to stimulated production of MMPs by the elevated tear osmolarity in dry eye remains to be determined.

Artificial nucleic acid circuits with precisely controllable dynamic and function have shown great promise in biosensing, but their utility in molecular diagnostics is still restrained by the inability to process genomic DNA directly and moderate sensitivity. To address this limitation, we present a CRISPR-Cas-powered catalytic nucleic acid circuit, namely, CRISPR-Cas-only amplification network (CONAN), for isothermally amplified detection of genomic DNA. By integrating the stringent target recognition, helicase activity, and trans-cleavage activity of Cas12a, a Cas12a autocatalysis-driven artificial reaction network is programmed to construct a positive feedback circuit with exponential dynamic in CONAN. Consequently, CONAN achieves one-enzyme, one-step, real-time detection of genomic DNA with attomolar sensitivity. Moreover, CONAN increases the intrinsic single-base specificity of Cas12a, and enables the effective detection of hepatitis B virus infection and human bladder cancer-associated single-nucleotide mutation in clinical samples, highlighting its potential as a powerful tool for disease diagnostics.

Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

PURPOSE: To evaluate to effect of experimental dry eye on ocular surface apoptosis. METHODS: Aqueous tear production and clearance were inhibited by systemic administration of scopolamine and exposure to an air draft for 12 days in 4- to 6-week-old 129SvEv/CD-1 mixed white mice. Eyes and ocular adnexa were excised, cryosectioned, and evaluated for apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemical assay for caspase-3 and poly(ADP-ribose) phosphate (PARP), and examination of nuclear morphologic changes by Hoechst DNA nuclear staining and transmission electron microscopy. RESULTS: The number of TUNEL-positive cells in the mice with induced dry eye was significantly increased compared with control mice in the following ocular regions: central corneal (P < 0.0014), peripheral corneal (P < 0.0001), bulbar conjunctival (P < 0.0021), and tarsal conjunctival (P < 0.0046) epithelia; tarsal conjunctival stroma (P < 0.0274); and lid margin (P < 0.0219, n = 4 in all cases). There were no significant differences observed between treated and control groups in the central corneal, peripheral corneal, or bulbar conjunctival stroma; meibomian glands; skin; retina-choroid; or episcleral regions. Immunohistochemistry for caspase-3 and poly(ADP-ribose) polymerase p85 fragment revealed increased immunoreactivity in regions of increased TUNEL positivity, particularly in the corneal and conjunctival epithelial cells. Ultrastructural morphologic changes consistent with apoptosis were observed in the conjunctival epithelial cells. CONCLUSIONS: Experimentally induced dry eye in mice causes apoptosis of cells in ocular surface tissues including the central and peripheral corneal epithelium, bulbar and tarsal conjunctival epithelia, tarsal conjunctival stroma, and lid margin. Apoptosis may play a key role in the pathogenesis of keratoconjunctivitis sicca and may be a therapeutic target for this condition.

Ferroptosis, a newly identified form of regulated cell death, is characterized by overwhelming iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Preventing cellular iron overload by reducing iron uptake and increasing iron storage may contribute to inhibit ferroptosis. Mitochondrial ferritin (FtMt) is an iron-storage protein that is located in the mitochondria, which has a significant role in modulating cellular iron metabolism. Recent studies showed that FtMt played inhibitory effects on oxidative stress-dependent neuronal cell damage. However, the potential role of FtMt in the progress of ferroptosis in neuronal cells has not been studied. To explore this, we established ferroptosis models of cell and drosophila by erastin treatment. We found that overexpression of FtMt in neuroblastoma SH-SY5Y cells significantly inhibited erastin-induced ferroptosis, which very likely was achieved by regulation of iron homeostasis. Upon erastin treatment, significant increases of cellular labile iron pool (LIP) and cytosolic ROS were observed in wild-type SH-SY5Y cells, but not in the FtMt-overexpressed cells. Consistent with that, the alterations of iron-related proteins in FtMt-overexpressed cells were different from that of the control cells. We further investigated the role of FtMt in erastin-induced ferroptosis in transgenic drosophila. We found that the wild-type drosophilas fed an erastin-containing diet didn't survive more than 3 weeks. In contrast, the FtMt overexpressing drosophilas fed the same diet were survival very well. These results indicated that FtMt played a protective role in erastin-induced ferroptosis.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

OBJECTIVE: Uncertainty exists over the size of potential beneficial effects of medical treatments targeting hematoma growth in intracerebral hemorrhage (ICH). We report associations of hematoma growth parameters on clinical outcomes in the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT1) (ClinicalTrials.gov NCT00226096). METHODS: In randomized patients with both baseline and 24-hour brain CT (n = 335), associations between measures of absolute and relative hematoma growth and 90-day poor outcomes of death and dependency (modified Rankin Scale score 3-5) were assessed in logistic regression models, with data reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 10.7 mL (1 SD) increase in hematoma volume over 24 hours was strongly associated with poor outcome (adjusted OR 1.72, 95% CI 1.19-2.49; p = 0.004). An association was also evident for relative growth (adjusted OR 1.67, 95% 1.22-2.27; p = 0.001 for 1 SD increase). The analyses were adjusted for age, sex, achieved systolic blood pressure, elevated NIH Stroke Scale score (≥ 14), hematoma location, baseline hematoma volume, intraventricular extension, antithrombotic therapy, baseline glucose, time from ICH to baseline CT scan, and time from baseline to repeat CT scan. A 1 mL increase in hematoma growth was associated with a 5% (95% CI 2%-9%) higher risk of death or dependency. CONCLUSION: Medical treatments, such as rapid intensive blood pressure lowering, could achieve ∼2-4 mL absolute attenuation of hematoma growth. There is hope that this could translate into modest but still clinically worthwhile (∼10%-20% better chance) outcome from ICH.

Knee osteoarthritis is a chronic degenerative disease. Cartilage and subchondral bone degeneration, as well as synovitis, are the main pathological changes associated with knee osteoarthritis. Mechanical overload, inflammation, metabolic factors, hormonal changes, and aging play a vital role in aggravating the progression of knee osteoarthritis. The main treatments for knee osteoarthritis include pharmacotherapy, physiotherapy, and surgery. However, pharmacotherapy has many side effects, and surgery is only suitable for patients with end-stage knee osteoarthritis. Exercise training, as a complementary and adjunctive physiotherapy, can prevent cartilage degeneration, inhibit inflammation, and prevent loss of the subchondral bone and metaphyseal bone trabeculae. Increasing evidence indicates that exercise training can improve pain, stiffness, joint dysfunction, and muscle weakness in patients with knee osteoarthritis. There are several exercise trainings options for the treatment of knee osteoarthritis, including aerobic exercise, strength training, neuromuscular exercise, balance training, proprioception training, aquatic exercise, and traditional exercise. For Knee osteoarthritis (KOA) experimental animals, those exercise trainings can reduce inflammation, delay cartilage and bone degeneration, change tendon, and muscle structure. In this review, we summarize the main symptoms of knee osteoarthritis, the mechanisms of exercise training, and the therapeutic effects of different exercise training methods on patients with knee osteoarthritis. We hope this review will allow patients in different situations to receive appropriate exercise therapy for knee osteoarthritis, and provide a reference for further research and clinical application of exercise training for knee osteoarthritis.

BACKGROUND: Traumatic fractures place a substantial burden on health-care systems worldwide. Although detailed information about incidence, distribution, and risk factors for traumatic fractures is vital for planning and prevention, in China, national data are unavailable. We aimed to do an up-to-date national survey on the population-weighted incidence of traumatic fractures in China. METHODS: The China National Fracture Study (CNFS) was a retrospective epidemiological study that recruited a nationally representative sample from eight provinces, 24 urban cities, and 24 rural counties in China using stratified random sampling and the probability proportional to size method. All eligible household members who had lived in their current residence for 6 months or longer were personally interviewed by trained research teams about traumatic fractures of the trunk, arms, or legs (not including the skull, sternum, and ribs) that had occurred in 2014. Telephone surveys were used for participants who were non-contactable after repeated visits. Fracture cases were verified by clinical records, medical history, and radiographs by orthopaedic surgeons and radiologists. We estimated incidence rates for traumatic fractures for the overall population and for subgroups by age and sex, as well as by demographic factors such as ethnic origin, occupation, geographical region, and residency category. We also studied potential associations between fractures and various factors of interest, such as age, ethnic origin, education, smoking, alcohol drinking, sleep time per day, and history of previous fracture. Data were weighted during statistical analysis to ascertain the national incidence rate. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR-EPR-15005878. FINDINGS: Between Jan 19, 2015, and May 16, 2015, 535 836 individuals were selected and invited to participate in the study. Questionnaires from 23 649 (4%) individuals were excluded due to missing items, insufficient responses, or logical errors. Following exclusions, 512 187 (96%) individuals participated in the CNFS, consisting of 259 649 (51%) boys and men and 252 538 (49%) girls and women. Of these individuals, 1763 individuals had experienced traumatic fractures during 2014 (n=1833). The population-weighted incidence rate of traumatic fractures of the trunk, arms, or legs was 3·21 (95% CI 2·83-3·59) per 1000 population in 2014 (3·65, 3·12-4·18 in men and 2·75, 2·46-3·04 in women). For all ages, sleeping less than 7 h per day was identified as a risk factor for traumatic fractures. We identified previous fracture history as a risk factor for adults aged 15 years and older. Alcohol consumption incurred a risk effect for men aged 15 years and older and women aged 15-64 years. INTERPRETATION: Our results provide detailed information about fracture incidence, distribution, and risk factors, which can now be used as an up-to-date clinical evidence base for national health-care planning and preventive efforts in China and elsewhere. Specific public health policies that focus on decreasing alcohol consumption, prohibiting drunk driving, promoting smoking cessation, and encouraging individuals to obtain sufficient sleep and maintain a healthy bodyweight should be urgently implemented to help reduce the risk of traumatic fractures. FUNDING: The Hebei Province Medical Science Special Major Projects Research Fund.

To identify risk factors for periprosthetic joint infection following primary total joint arthroplasty, a systematic search was performed in Pubmed, Embase and Cochrane library databases. Pooled odds ratios (ORs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Patient characteristics, surgical-related factors and comorbidities, as potential risk factors, were investigated. The main factors associated with infection after total joint arthroplasty (TJA) were male gender (OR, 1·48; 95% CI, 1.19-1.85), age (SMD, -0·10; 95% CI, -0.17--0.03), obesity (OR, 1·54; 95% CI, 1·25-1·90), alcohol abuse (OR, 1·88; 95% CI, 1·32-2·68), American Society of Anesthesiologists (ASA) scale > 2 (OR, 2·06; 95% CI, 1·77-2·39), operative time (SMD, 0·49; 95% CI, 0·19-0·78), drain usage (OR, 0·36; 95% CI, 0·18-0·74), diabetes mellitus (OR, 1·58; 95% CI, 1·37-1·81), urinary tract infection (OR, 1·53; 95% CI, 1.09-2.16) and rheumatoid arthritis (OR, 1·57; 95% CI, 1·30-1·88). Among these risk factors, ASA score > 2 was a high risk factor, and drain usage was a protective factor. There was positive evidence for some factors that could be used to prevent the onset of infection after TJA.

As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial-mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.

BACKGROUND: Previous studies have indicated that the performance of glomerular filtration rate (GFR) estimation equations vary according to the races of the target population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has not been validated in the Chinese population including patients with chronic kidney disease (CKD) and healthy controls. METHODS: A total of 977 adult persons (682 patients with CKD and 295 healthy volunteers) from nine renal institutes of university hospitals located in nine geographic regions of China were enrolled in the study. A diagnostic test study comparing the CKD-EPI two-level and four-level race equation, the Modification of Diet in Renal Disease (MDRD) Study equation and the modified MDRD equation for Chinese (the Chinese equation). The (99m)Tc- diethylenetriamine pentaacetic acid dual plasma clearance was used as a reference method for measuring GFR. RESULTS: The mean age of participants was 48.3 ± 16.0 years and 479 (49.0%) were male. The CKD-EPI two-level race equation and the Chinese equation performed better than the MDRD Study equation and CKD-EPI four-level race equation, with less bias (median difference between estimated GFR and reference GFR, 0.2 and 0.3 versus -2.4 and 3.0 mL/min/1.73 m(2)), improved precision (interquartile range of the difference, 20.5 and 20.8 versus 23.4 and 20.5 mL/min/1.73 m(2)) and greater accuracy (percentage of estimated GFR within 30% of reference GFR, 73.4 and 73.0% versus 69.8 and 70.1%). CONCLUSIONS: The CKD-EPI two-level race equation and the Chinese equation performed similarly in the Chinese population, and both performed better than the MDRD Study equation and the CKD-EPI four-level race equation.

To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.

The purpose of this study was to explore incidence and risk factors of adjacent segment disease (ASD) following posterior decompression and instrumented fusion for degenerative lumbar disorders, and hope to provide references in decision making and surgical planning for both spinal surgeon and surgically treated patients.By retrieving the medical records from January 2011 to December 2013 in our hospital, 237 patients were retrospectively reviewed. According to the occurrence of ASD at follow up, patients were divided into 2 groups: ASD and N-ASD group. To investigate risk values for the occurrence of ASD, 3 categorized factors were analyzed statistically: Patient characteristics: age, sex, body mass index (BMI), bone mineral density (BMD), duration. Surgical variables: surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, intraoperative superior facet joint violation. Radiographic parameters: preoperative lumbar lordosis, preoperative angular motion at adjacent segment, preoperative adjacent segment disc degeneration, preoperative paraspinal muscle degeneration.Postoperative ASD was developed in 15 of 237 patients (6.3%) at final follow up. There was no statistically significant difference between the 2 groups in patient characteristics of age, sex composition, BMD, duration, while the BMI was higher in ASD group than that in N-ASD group. There was no difference in surgical variables of surgical strategy, number of fusion level, surgery segment, surgery time, blood loss, while intraoperative superior facet joint violation was more common in ASD group than that in N-ASD group. There was no difference in radiographic parameters of preoperative lumbar lordosis, preoperative paraspinal muscle degeneration, while preoperative adjacent segment disc degeneration were more severe in ASD group than that in N-ASD group. The Logistic regression analysis revealed that, BMI >25 kg/m, preoperative disc degeneration, and superior facet joint violation were independently associated with ASD.In conclusion, higher BMI, preoperative disc degeneration at adjacent segment and intraoperative superior facet joint violation are risk factors for ASD. Patients who are overweight or obesity and with preoperative disc degeneration at adjacent segment should be fully informed the risk of ASD. For surgeons, it is essential to prevent superior facet joint violation in pedicle screw insertion procedure.

Histone deacetylase 5 (HDAC5) belongs to class II HDAC subfamily and is reported to be increased in the kidneys of diabetic patients and animals. However, little is known about its function and the exact mechanism in diabetic kidney disease (DKD). Here, we found that HDAC5 was located in renal glomeruli and tubular cells, and significantly upregulated in diabetic mice and UUO mice, especially in renal tubular cells and interstitium. Knockdown of HDAC5 ameliorated high glucose-induced epithelial-mesenchymal transition (EMT) of HK2 cells, indicated in the increased E-cadherin and decreased α-SMA, via the downregulation of TGF-β1. Furthermore, HDAC5 expression was regulated by PI3K/Akt signaling pathway and inhibition of PI3K/Akt pathway by LY294002 treatment or Akt phosphorylation mutation reduced HDAC5 and TGF-β1 expression in vitro high glucose-cultured HK2 cells. Again, high glucose stimulation downregulated total m6A RNA methylation level of HK2 cells. Then, m6A demethylase inhibitor MA2 treatment decreased Akt phosphorylation, HDAC5, and TGF-β1 expression in high glucose-cultured HK2 cells. In addition, m6A modification-associated methylase METTL3 and METTL14 were decreased by high glucose at the levels of mRNA and protein. METTL14 not METTL3 overexpression led to PI3K/Akt pathway inactivation in high glucose-treated HK2 cells by enhancing PTEN, followed by HDAC5 and TGF-β1 expression downregulation. Finally, in vivo HDACs inhibitor TSA treatment alleviated extracellular matrix accumulation in kidneys of diabetic mice, accompanied with HDAC5, TGF-β1, and α-SMA expression downregulation. These above data suggest that METTL14-regulated PI3K/Akt signaling pathway via PTEN affected HDAC5-mediated EMT of renal tubular cells in diabetic kidney disease.

BACKGROUND: Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis. METHODS: The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells. RESULTS: Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C. CONCLUSION: These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.

Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8(+) T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients' survival and metastasis.

BACKGROUND/OBJECTIVE: Inadvertent intraoperative hypothermia (core temperature <36°C) is a frequently preventable complication with several adverse consequences. Our study aimed to determine the overall incidence of inadvertent intraoperative hypothermia and its risk factors associated with clinical outcomes in this national survey in China. METHODS: We conducted a national cross-sectional study with 30 days postoperative follow-up from November 2014 through August 2015. A total of 3132 eligible patients underwent general anesthesia were randomly selected from 28 hospitals in the nationwide of China. RESULTS: The overall incidence of intraoperative hypothermia was as high as 44.3%, in which cumulative incidence rates of hypothermia being 17.8%, 36.2%, 42.5% and 44.1% within 1 h, 2 h, 3 h and 4 h respectively following induction of anesthesia. All patients were warmed passively by covering of surgical draping, sheets or cotton blankets, whereas only 14.2% of patients received active warming with space heaters or electric heater or electronic blankets. Compared to normothermic patients, patients with hypothermia is associated with more postoperative ICU admit, longer PACU and more postoperative hospital days, but no difference in surgical site infection (SSI) rates or 30-day mortality. Several factors were shown to be associated with decreased risk of hypothermia. They are active warming (OR = 0.46, 95% CI 0.26-0.81), BMI ≥ 25 (OR = 0.54, 95% CI 0.45-0.65), higher baseline core temperature (OR = 0.04, 95% CI 0.03-0.06), and higher ambient temperature (OR = 0.83, 95% CI 0.78-0.88). Risk factors associated with an increased risk of hypothermia included major-plus surgery (OR = 1.49, 95% CI 1.23-1.79), and long anesthesia (>2 h) (OR = 2.60, 95% CI 2.09-3.24). CONCLUSIONS: The incidence of intraoperative hypothermia in China is high, and the rate of active warming of patients during operation is low. Hypothermia is associated with more postoperative shivering, increased ICU admissions, and longer postoperative hospital days.