Predicting the risk of non-specific low back pain in the young population: development and assessment of a new predictive nomogram.

OBJECTIVE: Non-specific low back pain is a common disorder that affects more than 80% of the world's population. But the potential risk factors remain unclear. The aim of this study is to develop a nomogram for the risk prediction of low back pain in young population. PATIENTS AND METHODS: A total of 264 young participants (18-45 years old) were recruited and randomly divided into a training set (n=188) and a validation set (n=76) by a ratio of 7:3. The nomogram was developed based on the training set. The independent predictors of low back pain were identified by LASSO and logistic regression analysis. A nomogram was developed according to the predictors. To assess the reliability of the nomogram, the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were applied. The validation set was used to validate the results. RESULTS: Sixteen factors were included in the characteristics of the eligible subjects. LASSO showed that five independent predictors including working posture, exercising hours per week, Tuffier's line, six lumbar vertebrae anomaly, and lumbar lordosis angle were the independent risk factors of low back pain in young population, which were identified by multivariate logistic regression analysis and were used to establish the nomogram. The AUC values of the nomogram were 0.867 (95% CI: 0.809-0.924) and 0.868 (95% CI: 0.775-0.961) in the training and validation set, respectively. The calibration curve revealed that the prediction model of the nomogram was greatly consistent with the actual observation. In addition, the DCA indicated that the nomogram was clinically useful. CONCLUSIONS: Working posture, exercising hours per week, Tuffier's line, six lumbar vertebrae anomaly, and lumbar lordosis angle are identified as independent predictors of non-specific low back pain in young population. And the nomogram based on the above five predictors can accurately predict the risk of low back pain in young people.

[Effects of ultrasonic bone curettes combined with high-speed drills in posterior laminectomy and decompression procedure for severe thoracic spinal stenosis].

Objective: To evaluate the safety and efficacy of the combined use of ultrasonic bone curette with the high-speed drill in posterior laminectomy and decompression procedure for severe thoracic spinal stenosis, and propose the optimal cutting position for ultrasonic bone curette during the laminectomy. Methods: By observing and measuring the parameters of thoracic pedicle, lamina, inner wall of the vertebral canal and their relation with the surrounding structures on cadavers, we provided a morphological marker for laminectomy by an ultrasonic bone curette. Data of 19 patients with severe thoracic spinal stenosis treated by posterior laminectomy and decompression were collected from June 2017 to June 2018 in Shanghai Changzheng Hospital. There were 11 males and 8 females, aged (50±6) years. The patients received laminectomy with the combined use of ultrasonic bone curette and the high-speed drill (Group A, n=10) or the use of ultrasonic bone curette alone (Group B, n=9). Operational time of decompressive laminectomy, blood loss, as well as perioperative complications such as durotomy, cerebrospinal fluid leak, injury of the nerve root and spinal cord were recorded in these two groups. The improvement of symptoms and the decompression width of the spinal canal were evaluated after operation. Two independent samples t-test was used for the comparison of two sets of continuous normal distribution data. Results: We had done the measurement in 6 cadavers. The mean distance between the boundary of cancellous-cortical bone of lamina and the inner wall of spinal canal was (0.9±0.4) mm, and the distance between the boundary of cancellous-cortical bone of pedicle and the inner wall of the spinal canal was (1.2±0.6) mm. For the surgeries in groups A, the mean laminectomy time for each segment was (4.4±0.5) min, the mean width of posterior laminectomy was (21.8±0.5) mm; and for the surgeries in group B, the mean laminectomy time for each segment was (5.0±0.5) min, the mean width of posterior laminectomy was (19.9±1.0) mm; there were significant differences in laminectomy time for each segment and the width of posterior laminectomy between the two groups (t=-2.391, 3.491, both P<0.05). There was one case of dura injury and one case of thoracic nerve root injury during the operation in group B. Conclusions: It is safer and more reliable for the combined use of ultrasonic bone curette with the high-speed drill in posterior laminectomy and decompression procedure for the severe thoracic spinal stenosis. The interface between the cortical bone and the medial edge of cancellous bone of the pedicle could be identified as the cutting mark for ultrasonic bone curette in this procedure.

MiR-543-3p promotes locomotor function recovery after spinal cord injury by inhibiting the expression of tumor necrosis factor superfamily member 15 in rats.

OBJECTIVE: To explore the effect of miR-543-3p on the recovery of locomotor function after spinal cord injury (SCI) by regulating tumor necrosis factor superfamily member 15 (TNFSF15) mediated inflammation and apoptosis. MATERIALS AND METHODS: Macrophages were isolated from the abdominal cavity of 2-3 months old Sprague-Dawley (SD) rats and cultured. The levels of miR-543-3p, tumor necrosis factor superfamily member 15 (TNFSF15), TNF-like molecule 1A (TL1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) after transfection of miR-92b-5p into activated macrophages were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Moreover, the mRNA expressions of miR-543-3p, TNFSF15, TL1A and NF-κB after SCI in rats were detected by qRT-PCR. Meanwhile, the protein expressions of tumor necrosis factor (TNF-α), interleukin-1 ß (IL-1ß) and Caspase8 were detected by Western blot. After intrathecal injection of miR-543-3p mimics, the mRNA expressions of miR-543-3p, TNFSF15, TL1A and NF-κB and the protein expressions of TNF-α, IL-1ß and Caspase8 in spinal cord injured area of mice were measured by qRT-PCR and Western blot, respectively. Basso Beattie Bresnahan (BBB) locomotor rating scale was used to determine the recovery of locomotor function after spinal cord injury and injection of miR-543-3p mimics. RESULTS: Compared with inactivated cells, the expression of miR-543-3p in activated macrophages was significantly declined. However, the levels of TNFSF15, TL1A and NF-κB were significantly elevated. The expressions of TNFSF15, TL1A and NF-κB were remarkably downregulated after transfection of miR-543-3p. In addition, the level of miR-543-3p was significantly downregulated, accompanied by an increase in TNFSF15, TL1A and NF-κB in SCI rats. Accordingly, the protein levels of TNF-α and IL-1ß and Caspase8 were also significantly increased. However, the expressions of TNFSF15, TL1A and NF-κB were significantly down-regulated in rats injected with miR-543-3p mimics, whereas the protein levels of TNF-α and IL-1ß and Caspase8 were significantly suppressed. Finally, compared with SCI group, the recovery of locomotor function in miR-543-3p mimics administration group was significantly improved. CONCLUSIONS: After SCI, miR-543-3p can inhibit the activity of NF-κB by suppressing the inflammatory aggravation of TNFSF15 and decreasing its product TL1A. MiR-543-3p leads to the improvement of neuron protection and locomotor function via attenuating inflammatory reaction and cell apoptosis.

[Analysis of correlation between spinal nerve high tension and disc degeneration in 100 cases].

Objective: To explore the correlation between the spinal nerve high tension and lumbar disc degeneration, the pathogenesis of hanging intervertebral disc degeneration. Methods: From June 2016 to June , a retrospective analysis 2017 of 100 cases of lumbar spinal stenosis were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University. They were divided into experimental group (50 cases, nerve high tension group) and control group (50 cases, nervous tension in the normal group) according to preoperative lumbar MRI of cauda equina syndrome and settlement of intraoperative detecting nerve tension. The Pfirrmann grade was used to evaluate degree of lumbar (L3/4-L5/S1) disc degeneration.The correlation between spinal nerve tension and lumbar disc degeneration was analyzed, and the severity of experimental group and control group on lumbar disc degeneration was compared. Results: There was no significant difference in the age and sex ratio between the two groups (P>0.05). The Pfirrmann score of the experimental group was L3/4 (4.74±1.6) grade, L4/5 (5.32±1.33) grade, L5/S1 (5.54±1.13) grade; the control group Pfirrmann score was L3/4 (3.5±1.16) grade, L4/5 (4.12±0.9) grade, and L5/S1 (4.1±0.97) grade.The severity of intervertebral disc degeneration in experimental group was higher than that in control group, with statistical significance (P<0.05). There was a correlation between lumbar disc degeneration and nerve tension in L3/4, L4/5 and L5/S1, and the correlation trend was L5/S1> L4/5> L3/4. Conclusion: There is a correlation between lumbar disc degeneration and spinal nerve high tension.A new pathogenesis of hanging intervertebral disc degeneration that the degeneration of lumbar disc is a compensatory mechanism in order to alleviate the axial stretch injury is put forward.

Comparing effects of cervical anterior approach and laminoplasty in surgical management of cervical ossification of posterior longitudinal ligament by a prospective nonrandomized controlled study.

INTRODUCTION: The laminoplasty has been the most widely used surgical method for OPLL. In recent years, increasing attention has been drawn to the anterior operative approaches for surgical treatment of cervical OPLL. However, which method is the optimum selection for therapy of cervical OPLL is still obscure. Therefore, we performed this prospective nonrandomized clinical study in patients with multilevel cervical myelopathy due to OPLL and compare the therapeutic efficiency of laminoplasty and anterior approach (cervical discectomy and/or cervical corpectomy) in the management of multilevel cervical OPLL. HYPOTHESIS: There is no difference in clinical effects between anterior cervical spine surgery and laminoplasty in the treatment of multilevel cervical OPLL. MATERIAL AND METHODS: A total of 150 consecutive patients with multilevels of cervical OPLL underwent anterior approaches (ACDF, ACCF and HDF) from July 2010 to June 2014, which were enrolled in this study. During the same period, one hundred and two patients receiving the laminoplasty were enrolled in the study. The clinical effects, alignment and range of motion (ROM) of cervical spine in patients of the anterior group and posterior group were assessed, respectively. The effects of high signals in T2 weighed MRI scans and percentage of spinal canal stenosis in these patients were also evaluated. Finally, postoperative complications regarding each group were analyzed. RESULTS: Although significant differences in types of OPLL and preoperative sagittal alignment of cervical spine occurred in the two groups (P<0.05), clinical effects of the two groups were similar (P>0.05). The cervical curvature in laminoplasty group showed significant decrease at final follow-up (P<0.05). For ROM of cervical spine, no significant alteration was observed in both groups. The high T2 weighed signals and rate of spinal canal stenosis can influence clinical effects of both anterior group and laminoplasty group. In addition, significantly higher complication rate was observed in laminoplasty group compared with anterior group (P<0.05). DISCUSSION: Both anterior and laminoplasty approaches can be considered effective and safe procedures in the treatment of the multilevel OPLL. However, the anterior approach with relatively lower incidence of postoperative complications is a better choice for cases with poor cervical curvature and serious spinal canal stenosis. TYPE OF STUDY AND LEVEL OF PROOF: Level 3 nonrandomized, controlled clinical trials.

[Clinical diagnosis and management of cervical spondylotic amyotrophy].

Objective: To investigate the clinical characteristics and surgical treatment of cervical spondylotic amyotrophy. Methods: Thirteen patients(13 man) with proximal (10) and distal(3) cervical spondylotic amyotrophy between November 2014 and September 2016 were included in this study. The average age of the patients was 55 (range, 47-66) years. The sex, age, clinical course, type of amyotrophy, lesion segment and postdecompression improvement in muscle power were reviewed. Results: Of 13 cervical spondylotic amyotrophy patients, 9 were performed on with cervical disectomy, 2 were performed on with cervical posterior operation, 2 remainding patients received nonoperative treatment. Cervical spondylotic amyotrophy patients were followed up 6-22 (average 10.6) months, muscle power of 4 patients (all proximal-type)were improved completely (the average recovery time were 4.4 months), muscle power of 6 patients were improved uncompletely, 1 patients failed to improve, the 2 remainding patients received nonoperative treatment had no change. Conclusion: Cervical spondylotic amyotrophy as a rare type of cervical spondylotic disorder, It should distinguish cervical spondylotic amyotrophy from amyotrophic lateral sclerosis, especially in the early stage of amyotrophic lateral sclerosis. A surgical treatment is recommended as the first line of proximal-type CSA, especially those with serious compression. It is important that clinicians should be aware that distal-type CSA had a poor results, resulting in a lower lower satisfaction, especially those with no, or insignificant, sensory disturbance.

[Lumbosacral nerve bowstring disease].

Objective: To define a novel disease-lumbosacral nerve bowstring disease, and propose the diagnostic criteria, while capsule surgery was performed and evaluated in the preliminary study. Methods: From June 2016 to December 2016, a total of 30 patients (22 male and 8 female; mean age of 55.1±9.7 years) with lumbosacral nerve bowstring disease were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University.Lumbosacral nerve bowstring disease was defined as axial hypertension of nerve root and spinal cord caused by congenital anomalies, which could be accompanied by other lesions as lumbar disc herniation, spinal cord stenosis or spondylolisthesis, or aggravated by iatrogenic lesions, resulting in neurological symptoms.This phenomenon is similar to a stretched string, the higher tension on each end the louder sound.Meanwhile, the shape of lumbosacral spine looks like a bow, thus, the disease is nominated as lumbosacral nerve bowstring disease.All the patients underwent capsule surgery and filled out Owestry disability index (ODI) and Tempa scale for kinesiophobia (TSK) before and after surgery. Results: The mean surgery time was (155±36) min, (4.3±0.4) segments were performed surgery.The pre-operative VAS, TSK and ODI scores were (7.6±0.8), (52.0±10.3) and (68.4±12.7), respectively.The post-operative VAS, TSK and ODI scores were (3.3±0.4), ( 24.6±5.2) and (32.1±7.4)(P<0.05, respectively), respectively. Conclusion: The definition and diagnostic criteria of lumbosacral nerve bowstring disease was proposed.Capsule surgery was an effective strategy with most patients acquired excellent outcomes as symptoms relieved and quality of life improved.

[Rules of anatomic morphology changes between the vertebral artery tortuosity and transverse foramen].

OBJECTIVE: To explore the rules of the anatomic morphology between vertebral artery tortuosity and transverse foramen. METHODS: From January 2012 to December 2015, 60 patients with vertebral artery tortuosity by means of analyzing the image data and basic clinic information as the observation group, and 50 patients randomly selected exclusive of vertebral artery tortuosity, absence of vertebral artery, vertebral artery aneurysm, cervical decomposition incomplete deformity and oral cavity prosthesis artifacts as the control group, the basic clinical information was collected; the transverse foramen area (TF) and vertebral artery cross-sectional area (VA) of the vertebral artery were measured in the observation group and the control group; internal diameter of vertebral artery tortuosity, length of vertebral artery were measured and; twisting coefficient (s)of the vertebral artery was calculated.Then the difference of the above-mentioned statistics was acquired. RESULTS: The C4 TF (25.91±10.13) mm and C6 TF(31.93±17.91) mm of the affected segment of the observation group were significantly higher than those in the control group[(22.11±8.67) mm, (27.19±7.89) mm] (P<0.05); VA and TF were positively correlated.The average age[(68.25±12.03) years], blood pressure (45 cases)of the observation group and the proportion of the menopausal women (39 cases)were higher than those in the control group[(61.32±11.32) years, 23/22](P<0.05). CONCLUSIONS: The area of transverse foramen of C4 and C6 could be affected by vertebral artery tortuosity. It might be related to the occurrence of bone degeneration around C6 and C4.The risk factors of the expansion of the transverse foramen might be advanced age, hypertension and menopausal women.

Role of radiation therapy in lung cancer management - a review.

Lung cancer is the leading cause of cancer death worldwide. Furthermore, more than 50% of lung cancer patients are found affected by distant metastases at the time of diagnosis. On the other hand, 20% of these patients are without regional spread and are good candidates for surgical operation. The remaining 30% represent an intermediate group whose tumors have metastasized up to regional lymph nodes. These remain 30% are the most appropriate candidates for radiation therapy. These patients are also called as "locally advanced lung cancer" or stage III lung cancer patients. In these patients strategy of combination therapy viz. radiation therapy in combination with chemotherapy is also tried by various groups in the recent past for this better management. However, long-term survival is still poor with a 5-year survival in 5-25% of patients. During the last decades, there has been a development in radiation strategies. The present review article focuses on different approaches to optimize radiotherapy for these patients.

Association of TUSC3 gene polymorphisms with non-syndromic mental retardation based on nuclear families in the Qinba mountain area of China.

TUSC3 interacts with the protein phosphatase 1 and magnesium ion transport system, which plays an important role in learning and memory. Abnormal conditions of learning and memory are common clinical characteristics of mental retardation (MR). However, the association of TUSC3 genetic polymorphisms with MR remains unknown. A total of 456 DNA samples including 174 nuclear families containing MR were collected in the Qinba mountain area of China. The genotypes of eight tag single nucleotide polymorphisms of TUSC3 were evaluated with traditional genetic methods. Family-based association tests, transmission disequilibrium tests (TDTs), and haplotype relative risk (HRR) analyses were performed to investigate the association between genetic variants of the TUSC3 gene and MR. The genetic polymorphisms rs10093881, rs6530893, and rs6994908 were associated with MR (all P values <0.05) based upon the results of single-site TDT and HRR analyses. The haplotype block consisting of rs6530893 and rs6994908, harboring the sixth exon of TUSC3, was also associated with MR (all P values <0.05). This study demonstrated an association between genetic polymorphisms of the TUSC3 gene and MR in the Qinba mountain area, the sixth exon of which might contribute to the risk of MR. However, further studies are needed on the causal mechanisms in this association.

Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: a case study with ruxolitinib.

Physiologically based pharmacokinetic modeling was applied to characterize the potential drug-drug interactions for ruxolitinib. A ruxolitinib physiologically based pharmacokinetic model was constructed using all baseline PK data in healthy subjects, and verified by retrospective predictions of observed drug-drug interactions with rifampin (a potent CYP3A4 inducer), ketoconazole (a potent CYP3A4 reversible inhibitor) and erythromycin (a moderate time-dependent inhibitor of CYP3A4). The model prospectively predicts that 100-200 mg daily dose of fluconazole, a dual inhibitor of CYP3A4 and 2C9, would increase ruxolitinib plasma concentration area under the curve by ∼two-fold, and that as a perpetrator, ruxolitinib is highly unlikely to have any discernible effect on digoxin, a sensitive P-glycoprotein substrate. The analysis described here illustrates the capability of physiologically based pharmacokinetic modeling to predict drug-drug interactions involving several commonly encountered interaction mechanisms and makes the case for routine use of model-based prediction for clinical drug-drug interactions. A model verification checklist was explored to harmonize the methodology and use of physiologically based pharmacokinetic modeling.

N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside induces sedative and hypnotic effects via GAD enzyme activation in mice.

BACKGROUND AND PURPOSE: N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is an analog of N(6)-(4-hydroxybenzyl) adenine riboside (NHBA), which was originally isolated from Gastrodia elata Blume. Our laboratory has previously demonstrated that B2 can produce strong sedative and hypnotic effects, but the mechanism remains to be determined. There is evidence that gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the brain, plays a major role in sleep regulation, and participates in the sedative and hypnotic effects of B2. Therefore, we studied the interactions between B2 and several GABAergic neurochemical parameters based on the sedative and hypnotic effects of B2. EXPERIMENTAL APPROACH: The GABA and glutamic acid (Glu) in the mouse brain were derivatized with o-phthalaldehyde (OPA) and measured by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The GAD and GABA-T enzyme activities were determined by measuring GABA and NADH production, respectively. The sleep structure analyses were performed by EEG studies in mice. KEY RESULTS: B2 increased the GABA levels and GAD enzyme activity in the mouse hypothalamus and cortex. The EEG results confirmed that B2 significantly shortened the sleep latency and increased the amount of NREM sleep. The GAD enzyme inhibitor semicarbazide (SCZ) blocked the sedative and hypnotic effects of B2. CONCLUSIONS AND IMPLICATIONS: These findings suggest that the GAD enzyme plays a significant role in the sedative and hypnotic effects of B2. Therefore B2 may be a promising candidate for further clinical studies and the appropriate use of GAD agonist may be a promising approach for sleep disorders.

No association between FGD1 gene polymorphisms and intellectual developmental disability in the Qinba mountain area.

FGD1 encoding a guanine nucleotide exchange factor, specifically activates Rho GTPase cell division cycle 42 (Cdc42). Dysfunction of FGD1 causes Aarskog-Scott syndrome (MIM #305400), an X-linked disorder that may affect bone and intellectual development. However, the relationship between FGD1 and intellectual developmental disorders (IDD) remains unclear. The purpose of this study was to investigate the genetic association between the FGD1 polymorphism and IDD. Working with families from the Qinba mountain area where the occurrence of IDD is higher than the average in China, we analyzed 456 samples from 130 nuclear families, effectively controlling for stratification and environmental factors. Five SNP loci (rs2230265, rs7881608, rs2239809, rs6614244, and rs2284710) were selected that were well distributed within the FGD1 gene. Genotyping was performed through single-strand conformation polymorphism and restriction fragment length polymorphism. The data were analyzed with transmission disequilibrium tests. In the Qinba mountain area, no significant association was observed between IDD and allele or genotype frequencies, or the haplotype of the 5 SNP loci of the FGD1 gene. The results indicate that FGD1 may not be a monogenetic X-linked factor in IDD. Further studies are required to investigate its role in intellectual development based on its specific interactions with Cdc42 or other partner proteins contributing to IDD.

Differentiation of neonatal dorsal root ganglion-derived neural stem cells into oligodendrocytes after intrathecal transplantation into a cauda equina lesion model.

Cauda equina syndrome (CES) is characterized by varying patterns of low back pain, sciatica, lower extremity sensorimotor loss, and bowel and bladder dysfunction. The prognosis for complete recovery of CES is dependent on not only the time before surgical intervention with decompression but also the severity of the nerve damage. Delayed or severe nerve compression impairs the capability of nerve regeneration. Transplantation of neural stem cells (NSCs) may facilitate axon regeneration and functional recovery in a spectrum of neurological disorders. Our study shows that the NSCs derived from early postnatal dorsal root ganglion (DRG) are able to proliferate to form neurospheres and differentiate into O4(+) oligodendrocytes but not glial fibrillary acidic protein (GFAP(+)) astrocytes or ßIII-tubulin(+) neurons in vitro. After intrathecal transplantation into the lumbar spinal canal stenosis animal model, most of the GFP-expressing NSCs were induced to differentiate into oligodendrocytes in vivo. Although the recovery of sensorimotor function was not significantly improved in rats with transplantation therapy, our results implied that subarachnoid microinjection of NSCs may promote axon regeneration of DRG neurons in the cauda equina model after nerve injury.

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy.

We investigated a possible association of collagen IX tryptophan (Trp) alleles (Trp2 and Trp3) and smoking with cervical spondylotic myelopathy (CSM) in 172 Chinese patients and 176 age- and gender-matched controls. The smoking status was evaluated by smoking index (SI). The CSM cases had a significantly higher prevalence of Trp2 alleles (Trp2+) than controls (19.8 vs 6.2%, P = 0.002), but the prevalence of Trp3 alleles (Trp3+) was similar between the two groups (23.3 vs 21.6%, P = 0.713). Logistic regression analyses showed that the subjects with Trp2+ had a higher risk for CSM. We thus analyzed whether smoking status influenced the association between Trp2 alleles and CSM risk. Among Trp2+ subjects with an SI less than 100, the smoking status did not influence the effect of risk for SCM [odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 0.85-2.18, P > 0.05]. When SI increased from 101 to 300, the OR for CSM reached 3.34 (95%CI = 2.11-5.67, P = 0.011); when SI was more than 300, the OR for CSM reached 5.56 (95%CI = 3.62-7.36, P < 0.001). Among Trp2- subjects with SI more than 300, the OR for CSM increased 2.14 (95%CI = 1.15-4.07, P = 0.024). We found a significant association between the Trp2 alleles and CSM risk and smoking amplifies this risk, suggesting that smoking abstinence is important for reducing CSM occurrence in subjects with high genetic risk.

Polymorphisms of brain-derived neurotrophic factor associated with heroin dependence.

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. It also plays a role in the reward response to many drugs, including heroin. To identify genetic variants associated with heroin dependence, we compared four single nucleotide polymorphisms (SNPs, rs13306221, rs6265, rs56164415, and rs16917204) of the BDNF gene in 487 subjects with heroin dependence and 492 healthy individuals. The analysis revealed the G allele of rs6265 was significantly more common in heroin-dependent subjects than in the healthy controls (P=0.001 after Bonferroni correction). Among heroin-dependent individuals, the onset of dependence was significantly earlier in individuals with GG or GA genotypes compared to AA individuals (P<0.01). Additionally, we found that the G allele of rs13306221 was significantly more frequent in heroin-dependent subjects than in controls (P=0.005 after Bonferroni correction). These findings support a role of BDNF rs6265 and rs13306221 polymorphisms in heroin dependence and may guide future studies to identify other genetic risk factors for heroin dependence.

PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway.

It is increasingly clear that the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a negative regulator of neuronal cell survival. However, its molecular mechanisms remain poorly understood. Here we found that PTEN/mTOR is critical for controlling neuronal cell death after ischemic brain injury. Male rats were subjected to MCAO (middle cerebral artery occlusion) followed by pretreating with bpv (pic), a potent inhibitor for PTEN, or by intra-cerebroventricular infusion of PTEN siRNA. bpv (pic) significantly decreased infarct volume and reduced the number of TUNEL-positive cells. We further demonstrated that although bpv (pic) did not affect brain injury-induced mTOR protein expression, bpv (pic) prevented decrease in phosphorylation of mTOR, and the subsequent decrease in S6. Similarly, down-regulation of PTEN expression also reduced the number of TUNEL-positive cells, and increased phospho-mTOR. These data suggest that PTEN deletion prevents neuronal cell death resulting from ischemic brain injury and that its neuroprotective effects are mediated by increasing the injury-induced mTOR phosphorylation.

Chemical constituents of the brown alga Dictyopteris divaricata.

A novel sesquiterpene-substituted benzoic acid, named dictyvaric acid (1), together with nine known compounds (2-10), have been isolated from the brown alga Dictyopteris divaricata Okam. The structure of 1 was elucidated as 3-[(decahydro-2-hydroxy-2,5,5,8a-tetramethyl-1-naphthalenyl)-methyl]-4-hydroxybenzoic acid by spectroscopic methods, including IR, FABMS, HR-FABMS, 1D and 2D NMR techniques. All compounds were obtained from this species for the first time.

Bromophenols from the red alga Rhodomela confervoides.

Six new bromophenols, 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)pyrocatechol (1), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-hydroxymethyldiphenylmethane (2), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (3), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde (4), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde dimethyl acetal (5), and 3-bromo-4,5-dihydroxybenzoic acid methyl ester (6), together with eight known bromophenols, 3-bromo-4,5-dihydroxybenzaldehyde (7), 2,3-dibromo-4,5-dihydroxybenzyl alcohol (lanosol, 8), 2,3-dibromo-4,5-dihydroxybenzyl methyl ether (9), 2,3-dibromo-4,5-dihydroxybenzyl ethyl ether (10), 2,3-dibromo-4,5-dihydroxybenzylaldehyde (11), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (12), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethylpyrocatechol (13), and 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenyl methane (14), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by chemical and spectroscopic methods including IR, HRFABMS, and 1D and 2D NMR techniques.