Dynamic cervical flexion/extension atlantodental interval and functional outcome of the Harms technique for posterior C1/2 fixation: A retrospective analysis of 16 atlantoaxial subluxation cases in a tertiary medical center.

BACKGROUND: The aim of this study was to assess the relationship between the atlantodental interval (ADI) on dynamic flexion/extension cervical radiographs and functional outcomes of posterior spinal fixation by the Harms technique for atlantoaxial subluxation (AAS). Dynamic flexion/extension on cervical radiographs is a standard assessment for evaluation of C1/2 instability in AAS patients. Most studies focused on postoperative ADI and functional outcome, including pain and fusion rate; only few studies compared dynamic ADI change pre- to post-operatively. MATERIAL AND METHODS: Retrospectively, we reviewed the medical records of 16 patients who underwent posterior spinal fixation in our center from 2018 to 2019. We used dynamic cervical flexion/extension radiographs to assess the pre- to postoperative change at 12 months in ADI of flexion (ADIf), ADI of extension (ADIe), ADI between flexion/extension (ADIΔ), C1/2 fusion rate and functional outcomes measured by the modified Japanese Orthopaedic Association scale (mJOA scale). Postoperative CT at 3∼12 months assessed screw positioning on the Gertzbein and Robbins classification. RESULTS: In the 16 patients included in this study, ADIf, ADIe and ADIΔ were significantly reduced, from respectively 8.0mm, 5.0mm and 3.0mm preoperatively to 4.6mm, 3.8mm and 0.8mm at 12 months' follow-up. The fusion rate was 81% and the mJOA score recovery rate was 34.9±14.7%. Although the screw malposition rate was higher than in other studies in C1(10%) and C2(20%), there were no new neurologic deficits or worsening of symptoms at follow-up. CONCLUSIONS: The ADIΔ showed significant reduction, showing that the Harms technique of posterior spinal fixation can effective in maintaining the stability of the atlantoaxial joint and improving functional outcome.

[Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial].

Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% (P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % (P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95%CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% (P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% (P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L (P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L (P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group (P=0.320). Ratios of negative to positive were 7.43% and 10.61% (P=0.360), and ratios of positive to negative were 10.40% and 7.58% (P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% (P=0.371), and the incidence of adverse events was 76.60% and 77.70% (P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

[Intranuclear cytoplasmic autophagosomes cause specific nucleolysis and cell death of liver cancer cells and liver cells].

The structure and performance of nuclear cytoplasmic autophagosomes was explored. Seventeen cases of hepatocellular carcinoma and liver cells with other diseases from liver tissues were selected. The nuclear cytoplasm were isolated and degraded by the nuclear membrane. Damaged cytoplasm had damaged its own membrane and the surrounding nuclear tissues other than the nuclear membrane, leading to specific nucleolysis and cell death of liver cancer cells and liver cells.

A study on molecular mechanisms of adiposis induced by long-term treatment of high-fat and high-sucrose in C57BL/6J mice.

Adiposis is reputed as a twin disease of type 2 diabetes and greatly harmful to human health. In order to understand the molecular mechanisms of adiposis, the changes of physiological, pathological, epigenetic and correlative gene expression were investigated during the adiposis development of C57BL/6J mice induced by long time (9 months) high-fat and high-sucrose diet (HFSD) sustainably. The results showed that mRNA transcription level of the Leptin, Glut4 and Glut2 genes have been obviously changed, which exhibit a negative correlation with methylation on their promoter DNA. The results also revealed that HFSD induced higher level of DNA methyltransferase 1 (DNMT1) in fat tissue might play important role in regulating the changes of methylation pattern on Glut4 and Leptin genes, and which might be one of the molecular mechanisms for the adiposis development.

Therapeutic potential of amniotic fluid stem cells to treat bilateral ovarian dystrophy in dairy cows in a subtropical region.

Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti-inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein-Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein-Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast-like morphology. They were positive for ß-integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10-15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility.

[Evaluation of short-term effect of intense pulsed light combined with meibomian gland expression in the treatment of meibomian gland dysfunction].

Objective: To explore short-term effect of intense pulsed light (IPL) combined with meibomian gland expression in treating meibomian gland dysfunction (MGD). Methods: This study was a prospective, randomized, double-masked, controlled study. Forty-four MGD patients were enrolled in the study and received three consecutive IPL treatments with an interval of 4 weeks. One eye of each patient was randomly assigned as the study eye receiving the IPL therapy with an energy of 14-16 J/cm(2), and the fellow eye was as the control eye receiving a placebo therapy with 0 J/cm(2). Meibomian gland expression was immediately performed after the IPL treatment in both eyes. Efficacy was evaluated through assessment of the meibomian gland yielding secretion score (MGYSS) , SPEED questionnaire, tear film break-up time (TBUT), cornea fluorescein staining and infrared meibography. Safety was evaluated through best spectacle corrected visual acuity, intraocular pressure, slit lamp examination and fundus examination. These examinations were performed before and after each treatment. Results: Significant improvements were observed in the MGYSS and TBUT after IPL treatments (P<0.05). The improvements compared to the baseline of MGYSS at the upper eyelid in the treatment eyes were significantly higher than those in the control eyes after the first treatment (Z=-2.036, P=0.003). The improvements compared to baseline of MGYSS at the lower eyelid and the TBUT in the treatment eyes were significantly higher than those in the control eyes after the second treatment (Z=-2.999 and -2.036, respectively P=0.007 and 0.042, respectively). SPEED and cornea fluorescein staining were decreased in both eyes after IPL treatments, but there was no statistical difference between the two eyes. No obvious complication was observed in the study. Conclusions: IPL treatment combined with meibomian gland expression is an efficient and safe therapy, and can increase meibomian gland yielding secretion, increase the TBUT, relieve the symptoms and repair the corneal epithelium defects for MGD eyes. (Chin J Ophthalmol, 2017, 53: 675-681).

Structural correlates of trait impulsivity in patients with bipolar disorder and healthy controls: a surface-based morphometry study.

BACKGROUND: Patients with bipolar disorder (BD) frequently exhibit impulsive behaviors independent of their mood state, and trait impulsivity is increasingly recognized as a crucial BD biomarker. This study aimed to investigate structural correlates of trait impulsivity measured using the Barratt Impulsiveness Scale (BIS) in healthy controls (HCs) and patients with BD. METHOD: We recruited 59 patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched HCs (33.9 ± 7.4 years). Participants underwent structural magnetic resonance imaging and clinical evaluations, and their BIS scores were evaluated. An automated surface-based method (FreeSurfer) was used to measure cortical thickness and generate thickness maps for each participant. Brain-wise regression analysis of the association between cortical thickness and BIS scores was performed separately for BD and HC groups by using a general linear model. RESULTS: Patients with BD obtained significantly higher BIS scores than HCs. In HCs, higher BIS scores were associated with a thinner cortex in the left inferior, middle and medial frontal cortices. By contrast, in BD patients, higher BIS scores were associated with a thicker cortex in the right insula. Patients with BD showed a thinner cortex than HCs in all these four structures. CONCLUSIONS: The findings indicate that the left prefrontal cortex plays a cardinal role in trait impulsivity of healthy individuals. Patients with BD have a different structural correlate of trait impulsivity in the right insula. However, the use of various psychotropics in patients with BD may limit our interpretation of BD findings.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

The prevalence of actinic keratosis in patients visiting dermatologists in two hospitals in China.

BACKGROUND: Actinic keratosis (AK) is one of the most common conditions treated by dermatologists in western countries. Studies have shown that AK prevalence in Europe, the U.S.A. and Australia is 4·5-60%. No data of AK prevalence in China has been reported. OBJECTIVES: This study aimed to explore the prevalence of AK in patients visiting dermatologists in two hospitals in China. METHODS: This study was conducted in the dermatology departments of two teaching hospitals (Peking University First Hospital, Beijing, and Fourth Military Medical University, Xi'an). All records for 5 years between 2008 and 2012 with clinically or pathologically diagnosed AKs were collected from the pathological databases of both hospitals. Data from these records were used to calculate the prevalence of AKs among patients who were seen by dermatologists in these hospitals. To estimate the reliability of data from the previous database, a cross-sectional study was conducted simultaneously in the two hospitals from 15 October to 8 December in 2012 after all dermatologists in the two departments were retrained through intensive courses on recognizing AK clinically. RESULTS: The prevalence of total clinical AKs through 2008-2012 was 0·52% in 1 590 817 patient visits in the two hospitals. The yearly prevalence of clinical AKs was 0·30-1·20%. In the cross-sectional study, 72 437 clinical patients were screened and 76 patients (1·05%) were identified to have clinically recognized AK. CONCLUSIONS: The overall prevalence of AKs in patients visiting dermatologists in the two hospitals in China was 0·52%, which is much lower than the prevalence in western countries.

Computer modelling integrated with micro-CT and material testing provides additional insight to evaluate bone treatments: Application to a beta-glycan derived whey protein mice model.

The primary aim of this study was to evaluate the influence of a whey protein diet on computationally predicted mechanical strength of murine bones in both trabecular and cortical regions of the femur. There was no significant influence on mechanical strength in cortical bone observed with increasing whey protein treatment, consistent with cortical tissue mineral density (TMD) and bone volume changes observed. Trabecular bone showed a significant decline in strength with increasing whey protein treatment when nanoindentation derived Young׳s moduli were used in the model. When microindentation, micro-CT phantom density or normalised Young׳s moduli were included in the model a non-significant decline in strength was exhibited. These results for trabecular bone were consistent with both trabecular bone mineral density (BMD) and micro-CT indices obtained independently. The secondary aim of this study was to characterise the influence of different sources of Young׳s moduli on computational prediction. This study aimed to quantify the predicted mechanical strength in 3D from these sources and evaluate if trends and conclusions remained consistent. For cortical bone, predicted mechanical strength behaviour was consistent across all sources of Young׳s moduli. There was no difference in treatment trend observed when Young׳s moduli were normalised. In contrast, trabecular strength due to whey protein treatment significantly reduced when material properties from nanoindentation were introduced. Other material property sources were not significant but emphasised the strength trend over normalised material properties. This shows strength at the trabecular level was attributed to both changes in bone architecture and material properties.

Association of gene polymorphisms in RANKL/RANK/OPG system with hypertension and blood pressure in Chinese women.

Recent studies have revealed that the receptor activator of nuclear factor-kappa B ligand/RANK/osteoprotegerin (RANKL/RANK/OPG) system has an important role in vascular calcification, which is contributory to various cardiovascular diseases and intimately linked to the regulation of blood pressure. Therefore, we performed a case-control study to investigate the associations of 21 single-nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A and TNFRSF11B genes in the RANKL/RANK/OPG system with hypertension and blood pressure in post-menopausal Chinese women. In this study, 503 hypertensive patients and 509 normal controls were recruited. Genotyping was performed using the high-throughput Sequenom genotyping platform. The results showed that two SNPs (rs6567270 and rs4603673) in the TNFRSF11A were associated with hypertension (P=0.010 and P=0.013, respectively) and systolic blood pressure (P=0.024 and P=0.023, respectively). One SNP (rs9646629) in the TNFRSF11A showed significant association with diastolic blood pressure (P=0.031). The results of this study suggest that TNFRSF11A but not TNFSF11 and TNFRSF11B genetic variation is associated with hypertension and blood pressure in Chinese women. The findings provide additional support for the genetic role of RANKL/RANK/OPG system in hypertension and blood pressure regulation.

Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women.

UNLABELLED: Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. INTRODUCTION: The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women. METHODS: A cross-sectional study was conducted in 881 post-menopausal women aged 50-89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations. RESULTS: Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = -0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917). CONCLUSIONS: Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.

Progranulin promotes Temozolomide resistance of glioblastoma by orchestrating DNA repair and tumor stemness.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults with a dismal prognosis. Current therapy of surgical removal combined with Temozolomide (TMZ) and radiation therapy only slightly prolongs the survival of GBM patients. Thus, it is essential to elucidate mechanism underlying its highly malignant properties in order to develop efficacious therapeutic regimens. In this study, we showed that progranulin (PGRN) was overexpressed in most GBM cell lines and the majority of human tumor samples. PGRN overexpression conferred GBM cells with tumorigenic properties and TMZ resistance by upregulating DNA repair (PARP, ATM, BRCA1, Rad51, XRCC1 and so on) and cancer stemness (CD133, CD44, ABCG2) genes, in part via an AP-1 transcription factor, specifically cFos/JunB. Curcumin, an AP-1 inhibitor, was also found to regulate PGRN promoter activity and expression including its downstream effectors aforementioned. These data suggested a feedforward loop between PGRN signaling and AP-1. PGRN depletion significantly decreased unlimited self-renewal and multilineage differentiation and the malignant properties of GBMs cells S1R1, and enhanced their vulnerability to TMZ. In addition, S1R1 depleted of PGRN also lost the ability to form tumor in an orthotopic xenograft mouse model. In conclusion, PGRN had a critical role in the pathogenesis and chemoresistance of GBM and functioned at the top of the hierarchy of cellular machinery that modulates both DNA repair pathways and cancer stemness. Our data suggest that a new strategy combining current regimens with compounds targeting PGRN/AP-1 loop like curcumin may significantly improve the therapeutic outcome of GBM.

Frequency and features of TP53 mutation in 30 Chinese patients with sporadic basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is a prevalent form of nonmelanoma skin cancer. Although numerous studies in white populations suggest that mutations in the TP53 gene play an important role in the development of BCC, it is not clear whether this is also the case in East Asian populations such as in China. AIM: To investigate the frequency and the features of TP53 mutation in sporadic BCC in a Chinese population. METHODS: In total, 30 patients with sporadic BCC, who had previously taken part in a study on PTCH1 mutations, were enrolled. BCC and control cells were obtained by laser-capture microdissection, and DNA was amplified and sequenced for analysis of TP53 mutations. RESULTS: In the 30 BCC samples, 6 TP53 point mutations were found (frequency of 20%), and 4 of these 6 mutations had ultraviolet (UV)-specific alterations. Combining these results with those of the previous study on PTCH1 mutations, we found that two patients with had three types of genetic alterations (each had two PTCH1 mutations and one TP53 point mutation). A further two patients each had one PTCH1 mutation and one UV signature TP53 mutation. In addition, the total number of UV-specific mutations of PTCH1 and TP53 accounted for 20% of the total patient group. CONCLUSIONS: The incidence of TP53 mutation in BCC in our Chinese subjects was lower than that reported for white populations. Many of the patients carried mutations of other genes in addition to of TP53. The majority of TP53 mutations were UV-induced specific alterations. However, the results of the two studies on TP53 and PTCH1 indicated that the incidence of UV-specific mutations is much lower in Chinese than in white populations.

Polymorphisms in the promoter region of myostatin gene are associated with carcass traits in pigs.

Higher average daily gain, more lean meat yield and less fat yield of porcine carcass increase selling profits for animal producers. Myostatin (MSTN), previously called GDF8, is a member of transforming growth factor-ß (TGF-ß) superfamily. It is a negative regulator for both embryonic development and adult homeostasis of skeletal muscle. In this study, the genotypes of the previously described SNPs MSTN g.435G>A and g.447A>G SNPs in 66 Duroc pigs, 33 Landrace pigs, 180 Duroc × Landrace (DL) pigs and 155 Duroc × Yorkshire × Landrace (DYL) pigs were determined by Taqman SNP Genotyping Assays. For Duroc and Landrace pigs, MSTN g.435GG/g.447AA individual had greater backfat thickness (p < 0.05) than g.435AA/g.447GG individual, whereas MSTN g.435AA/g.447GG had greater meat (p < 0.05) and meat percentage (p < 0.05) than g.435GA/g.447AG individual. For DL and DYL pigs, the MSTN g.435GG/g.447AA animals were greater in backfat at ultrasound 10th rib (p < 0.05) and carcass 10th rib (p < 0.01) than g.435AA/g.447GG individual. The MSTN g.435AA/g.447GG individual also had higher values than g.435GG/g.447AA for anterior-end meat (p < 0.05), posterior-end meat (p < 0.01), total meat weight (p < 0.01) and meat percentage (p < 0.01). This study confirmed evidence that MSTN g.435G>A and g.447A>G affected carcass traits in pigs. The effects of the mutated alleles were additive with the maximal effects resulting from two copies of the mutated allele. Selection for MSTN g.435A/g.447G allele is expected to increase muscle of limb and total meat production and decrease backfat thickness.