Therapeutic dosage of ozone inhibits autophagy and apoptosis of nerve roots in a chemically induced radiculoneuritis rat model.

OBJECTIVE: Radiculoneuritis characterizes by the neurogenic pain along the back of patients. This study aims to investigate the therapeutic effects of ozone on radiculoneuritis and the associated mechanisms in rat models. MATERIALS AND METHODS: A chemical radiculoneuritis rat model was successfully established. The rats were divided into 3 groups, including radiculoneuritis Model rats group (Model group, n=18), Ozone therapy group (n=18), and Normal control group (n=18). Ozone was administered at a dosage of 1 mg/kg/day. The electron microscope was used to observe autophagosomes in the cytoplasm. Immunohistochemistry assay was performed to examine cleaved caspase 3 and double-labeled immunofluorescence assay was used to detect light chain 3B (LC3B) and neuronal nuclear antigen (NeuN) expression. Quantitative Real-time PCR (RT-PCR) and Western blot were employed to evaluate the expression of LC3B, Beclin 1, phosphodiesterase 2A (PDE2A), and nuclear factor-kB p65 (NF-kBp65). RESULTS: Ozone significantly decreased autophagosomes formation and inhibited autophagy of nerve root cells in radiculoneuritis rat model. Ozone significantly decreased levels of autophagosomes initiator, LC3B, compared to Model group (p<0.05). Ozone significantly decreased cleaved caspase 3 expressions and alleviated apoptosis of nerve root cells compared to that of Model group (p<0.05). According to RT-PCR and Western blot assay, ozone significantly suppressed LC3B and Beclin 1 expression compared to that of Model group (p<0.05). Ozone significantly decreased PDE2A and NF-kB p65 expression compared to that of the Model group (p<0.05). CONCLUSIONS: Therapeutic dosage of ozone inhibits autophagy by suppressing LC3B and Beclin 1 expression and reduces apoptosis by blocking NF-kB signaling pathway.

[Utilization of Quality-of-life assessment Questionnaires for Intermittent Exotropia in China].

OBJECTIVE: To evaluate the reliability and validity of Chinese version of Quality-of-life assessment Questionnaires for Intermittent Exotropia (CIXTQ). METHODS: Cross-sectional study. The original English version of the IXTQ was translated into Chinese. The final Chinese version of the IXTQ (CIXTQ) consists of 3 parts: the 12-item child CIXTQ (for children ≥5 and<8 years old and ≥8 and<18 years old, respectively, to assess their health quality of life (HRQoL)), the 12-item proxy CIXTQ (for parents to assess children's HRQoL), and the 17-item parent CIXTQ (containing functional, psychosocial, and surgery subscales; for parents to assess their HRQoL). 175 IXT children and 151 control children along with one of their parents were recruited to answer the CIXTQ. Cronbach's α coefficient and split-half reliability were used to test the internal consistency reliability of the CIXTQ. Kappa coefficient was used to assess the test-retest reliability. Scale-level content validity index/average (S-CVI/Ave) was used to evaluate the content validity of the CIXTQ. Principal component analysis (PCA) was used to verify the construct validity of the parent CIXTQ. Comparison of different CIXTQ scores in IXT patients with controls was conducted by independent-samples t test to evaluate the discriminate validity of the CIXTQ. RESULTS: For all scales and subscales of the CIXTQ in different age groups, the Cronbach's α ranged from 0.804 to 0.963; the split-half reliability ranged from 0.658 to 0.963 and was higher than 0.7 except for the proxy CIXTQ for children aged ≥5 and<8 years old; the test-retest reliability ranged from 0.569 to 0.944. The S-CVI/Ave of the child, proxy and parent CIXTQ was 0.988, 0.988 and 0.966, respectively. Principal factors identified by PCA for the parent CIXTQ could be regrouped into the originally described 3 subscales which was functional, social psychology and surgery in different age groups. The mean scores of all the scales and subscales among IXT children and their parents (8.0±12.5-81.6 ±15.1) were significantly lower than these among control children and their parents (83.1±11.3-99.6±1.2) (t values range from -50.36 to -6.93, P<0.001). CONCLUSIONS: The CIXTQ are useful tools to evaluate the influence of IXT on HRQoL among Chinese children and their parents. (Chin J Ophthalmol, 2016, 52: 596-603).

Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and NF-κB/p65 and cytokine signals, but not p38, in a rat model of non-compressive lumbar disc herniation.

Inflammatory response induced by protrused nucleus pulposus (NP) has been shown to play a crucial role in the process of radicular pain. Lipoxins represent a unique class of lipid mediators that have anti-inflammatory and pro-resolving action. The present study was undertaken to investigate if intrathecal lipoxin A4 (LXA4) could alleviate mechanical allodynia in the rat models of application of NP to the L5 dorsal root ganglion (DRG). Non-compressive models of application of NP to L5 DRG were established and intrathecal catheterization for drug administration was performed in rats. Daily intrathecal injection of vehicle or LXA4 (10ng or 100ng) was performed for three successive days post-operation. Mechanical thresholds were tested and the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns were removed for the determination of tumor necrosis factor-α (TNF-α), IL-1ß, transforming growth factor-ß1 (TGF-ß1) and IL-10 expression and NF-κB/p65, extracellular signal-regulated kinase (ERK), C-Jun N-terminal kinase (JNK) and P38 expression. Application of NP to DRG in rats induced mechanical allodynia, increased the expression of pro-inflammatory factors (TNF-α and IL-1ß), NF-κB/p65, the phosphorylated-ERK (p-ERK), -JNK (p-JNK) and -P38 (p-p38) and decreased the expression of anti-inflammatory cytokines (TGF-ß1 and IL-10) in the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns. Intrathecal injection of LXA4 alleviated the development of neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF-α and IL-1ß), upregulated the expression of anti-inflammatory cytokines (TGF-ß1 and IL-10) and attenuated the activation of NF-κB/p65, p-ERK, p-JNK, but not p-p38, in a dose-dependent manner. In this study, we have demonstrated that LXA4 potently alleviate radicular pain in a rat model of non-compressive lumbar disc herniation. The anti-inflammatory and pro-resolution properties of LXA4 have shown a great promise for the management of radicular pain caused by intervertebral disc herniation.

Equations of state, transport properties, and compositions of argon plasma: combination of self-consistent fluid variation theory and linear response theory.

A consistent theoretical model that can be applied in a wide range of densities and temperatures is necessary for understanding the variation of a material's properties during compression and heating. Taking argon as an example, we show that the combination of self-consistent fluid variational theory and linear response theory is a promising route for studying warm dense matter. Following this route, the compositions, equations of state, and transport properties of argon plasma are calculated in a wide range of densities (0.001-20 g/cm(3)) and temperatures (5-100 kK). The obtained equations of state and electrical conductivities are found in good agreement with available experimental data. The plasma phase transition of argon is observed at temperatures below 30 kK and density about 2-6g/cm(3). The minimum density for the metallization of argon is found to be about 5.8 g/cm(3), occurring at 30-40 kK. The effects of many-particle correlations and dynamic screening on the electrical conductivity are also discussed through the effective potentials.

Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Vitamin D is a multifunctional pro-hormone and has widespread actions in human body. Several studies showed a possible association between vitamin D deficiency and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes, but no definite conclusion was available. METHODS: A systematic review and meta-analysis was performed to comprehensively assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels and DPN in patients with type 2 diabetes. Data from eligible studies were pooled using meta-analysis. RESULTS: Six studies that involved a total of 1,484 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis showed that there were obviously decreased serum 25(OH)D levels in DPN patients [weighted mean difference (WMD) = -6.36 ng/ml, 95 % confidence interval (95 % CI) -8.57 to -4.14, P < 0.00001]. Vitamin D deficiency was also significantly associated with increased risk of DPN in patients with type 2 diabetes [odds ratio (OR) 2.88, 95 % CI 1.84-4.50, P < 0.00001]. Meta-analysis of three studies with adjusted estimates showed that vitamin D deficiency was independently associated with increased risk of DPN in patients with type 2 diabetes (OR 2.68, 95 % CI 1.67-4.30, P < 0.0001). Sensitivity analysis showed that there was no obvious change in the pooled estimates. CONCLUSION: Vitamin D is involved in the development of DPN in type 2 diabetic patients, and vitamin D deficiency is very likely to be associated with DPN in type 2 diabetic patients. Further studies are needed to validate the association between vitamin D deficiency and DPN.

Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB.

BACKGROUND: Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-kappaB antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal hyperalgesia in a chronic constriction injury (CCI) model of rats. METHODS: Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI model was established. Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF-kappaB were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-kappaB p65 expression was assessed by western blot. RESULTS: CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-kappaB p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia. CONCLUSION: The activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.

[Locating the impairment of human cognitive function during hypoxia].

Objective. To find the location where the human brain cognitive function impairs under hypoxia. Method. 14 healthy males, aged 18-20 years, performed auditory Oddball test of two different intensities (55 dB, 80 dB) during exposure to 5000 m by breathing low oxygen mixture. EEG and Reaction Time (RT) were recorded. P3, the component of ERP, was extracted from EEG. P3 latency and RT were used as indices of the experiment. Additive Factors Method was used to analyse the result of the experiment. Result. Interaction between hypoxia and stimulus intensity was found for P3 latency and RT. Conclusion. Acute hypoxia influences the preprocessing stage of information processing.

[Effects of sleep deprivation on human performance].

Objective. To investigate the effects of sleep deprivation (SD) on human performance. Method. 8 healthy male college students participated the test. During 26 h of continuous awakeness (from 6:00 to 8:00 the next day), the volunteers were demanded to perform a battery of tests at 9 different time (7:00, 12:00, 16:00, 20:00, 0:00, 2:00, 4:00, 6:00, 8:00). The tests include: (1) single task: aural Oddball response, the response time (RT1) and correct rate (CR1) were recorded; (2) dual tasks: manual tracking and aural Oddball response, the response time (RT2), tracking error (ER) and correct rate (CR2) were recorded; (3) The Stanford sleepiness scale and subjective ratings of task difficulty access. Result. SD had significant effects on CT1, CT2 and ER (P=0.0001, P=0.00001, P=0.0004 respectively); SD increased RT1, RT2, ER at night time. SD had significant effects on SR, SSS score (P=0.0001, P=0.0000 respectively); SD increased SR, SSS score at night time. Since the subjects changed their response strategy, CR1 and CR2 were not influenced by SD at night time. Conclusion. SD has significant effects on response time, tracking error, subjective difficulty of cognitive tasks and subjective sleepiness.

Preliminary crystallographic studies of crotin II.

Crotin II isolated from the seeds of Euphorbiacea Croton tiglium has been crystallized. Crystals were grown by vapor diffusion using KCl as the precipitant. The crystal of crotin II belongs to the space group P6(1) or P6(5) with cell parameters a = b = 94.62 A, c = 28.43 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains one molecule of 15,000 Da. A data set to 1.82 A has been collected on an area detector.

The crystal and molecular structure of trichosanthin at 2.6 A resolution.

The crystallographic refinement of trichosanthin has been performed at 2.6 A resolution. The crystal and molecular structure of trichosanthin is described in detail in this paper. On summarizing the regularity of the amino acid sequences of eight kinds of ribosome inactivating proteins and combining with the crystal and molecular structure of trichosanthin, fifteen most conservative amino acid residues are analyzed. It is found that four most conservative polar amino acid residues Gln156, Glu160, Arg163 and Glu189 gather on the molecular surface on the boundary of the large and small domains, thus forming the active center of the protein molecule.

Crystallographic refinement of trichosanthin at 2.6A resolution.

The molecule model of trichosanthin has been rebuilt by using the electron density map improved by the solvent flatten and in accordance with the primary structure put forward by Collins. The crystallographic refinement of two trichosanthin molecules (3828 nonhydrogen atoms) in an asymmetric unit has been carried out by means of the restrain least-square procedure and diffraction data to a resolution of 2.6 A. The results are: an R factor 0.223 and the r.m.s. deviation of the bond length = 0.023 A. The new molecular model is in good agreement with the electron density map calculated with the coefficient 2Fo-Fc.

The three-dimensional structure of trichosanthin molecule.

A model completed recently of two trichosanthin molecules in an asymmetric unit belonging to the monoclinic system is reported. It can be seen that the molecular structure consists of two domains, one large and one small, and that there are some features in the secondary structure. The dissimilarity between two molecules as well as their interactions in an independent unit correlated in a non-symmetric way has been described, moreover, the binding sites of the heavyatom position in the derivatives are also discussed.