[Screening of phenylketonuria and analysis of phenylalanine hydroxylase gene in 380 996 newborns from Hainan province].

Objective: To investigate the incidence of phenylketonuria and distribution characteristics of phenylalanine hydroxylase (PAH) gene in newborns from Hainan province. Methods: Dry blood spot specimens of heels from 380 996 newborns in Hainan province from January 2017 to December 2019 were collected. Phenylalanine (Phe) concentrations in these dry blood spots were measured by the fluorescence method to screen phenylketonuria (PKU). A second dry blood spot sample will be collected if suspicious samples were detected after initial screening. Tandem mass spectrometry were used to detect the concentrations of Phe and tyrosine. Urine samples of the suspected newborns were sent out for urotrexate spectrum analysis and tetrahydrobiopterin loading test. PCR and flow-through rapid hybridization method were employed to detect PAH gene mutations. Meanwhile, peripheral blood samples of suspicious newborns of PKU and their parents were collected to perform gene sequencing. Results: Among the 380 996 newborns, 39 were suspected and 14 were diagnosed with PKU, including 11 cases of PAH deficiency and 3 cases of tetrahydrobiopterin deficiency. Of 14 confirmed cases, there were 8 male cases and 6 female cases. In the newborn population of Hainan province, the annual incidence of PKU was 1.22/100 000. Thirteen PAH gene mutations were detected in confirmed cases: c.728G>A, c.158G>A, c.1238G>C, c.611A>G, c.1068C>A, c.706+5G>A, c.740G>T, c.1081A>T, c.793T>G, c.1223G>A, c.721C>T, c.331C>T and c.1174T>A. Conclusions: PKU has a high incidence in newborn population of Hainan province in the past three years. The PAH gene has a wide spectrum of mutations. Two rare mutations were also found: c.793T>G and c.706+5G>A.

Effects of calcitriol on experimental spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To evaluate the effects of calcitriol on oxidative stress, apoptosis, autophagy and locomotor recovery in rats after spinal cord injury (SCI). SETTING: China. METHODS: Ninety female rats were randomly divided into three groups. Laminectomy only was performed in the control group. The SCI group received laminectomy as well as spinal cord compression injury. In the calcitriol group, SCI rats received an intraperitoneal injection of calcitriol (2 µg kg(-1)day(-1)). Oxidative stress was assessed by the tissue superoxide dismutase (SOD) activity and the contents of glutathione (GSH) and malondialdehyde (MDA). The extent of apoptosis was assessed by immunohistochemistry for C-caspase3, TUNEL staining and western blotting for C-caspase3, Bax and Bcl2. Transmission electron microscopy was used to examine autophagosomes in the injured spinal cord of calcitriol-treated rats. Autophagy was detected by western blotting for LC3-II, Beclin1 and p62. Histological changes were assessed by haematoxylin and eosin staining and Nissl staining. Functional recovery was reflected by the Basso, Beattie and Bresnahan locomotion rating scale and the inclined plane test. RESULTS: With calcitriol treatment, oxidative stress was decreased, SOD activity and GSH content were increased and MDA content was decreased. Moreover, apoptosis was inhibited in the SCI plus calcitriol group. However, a higher level of autophagy was detected in the lesions of the calcitriol group compared with the SCI group. Histological damage and neuron loss after SCI were reduced in calcitriol-treated rats, and functional recovery was significantly promoted in the calcitriol group compared with controls. CONCLUSIONS: Calcitriol promotes locomotor recovery after SCI by reducing oxidative stress and inhibiting apoptosis, as well as promoting autophagy.

Correlative study between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm.

In this study, we investigated the correlation between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm (MPN) using real-time fluorescence quantitative PCR. The incidence of thrombus was monitored and blood and coagulation were routinely assayed in patients with MPN. The JAK2V617F mutation was found in 8/68 individuals in the control group (11.8%); it was expressed in 44/68 patients with MPN (64.7%), suggesting that the rate of this mutation was significantly higher in patients with MPN than that in the control group. Twenty-six MPN patients (38.2%) showed symptoms of thrombosis; MPN patients with thrombosis showed a significantly higher rate of the JAK2V617F mutation, were of a greater age, and had higher blood pressure than MPN patients without thrombosis. In addition, the white blood cells (WBC) (21.98 ± 1.95) and platelets (364.68 ± 97.72) were significantly higher in patients, expressing the mutated gene, with polycythemia vera than in the patients without the mutation. The WBC (32.89 ± 4.25) and hemoglobin (161.92 ± 16.19) were significantly increased in the essential thrombocythemia patients with gene mutation compared with the patients without mutation. MPN patients showed higher blood clotting ability than the control subjects; moreover, MPN patients with the JAK2V617F mutation showed higher blood clotting ability than those without the mutation. The findings of this study indicate that the JAK2V617F mutation is correlated with the incidence of thrombosis, and analysis of this mutation has important clinical significance in the diagnosis and treatment of MPN.

Prognostic value of epidermal growth factor receptor amplification and EGFRvIII in glioblastoma: meta-analysis.

OBJECTIVES: Epidermal growth factor receptor (EGFR) gene amplification and the EGFRvIII mutation may have prognostic value in patients with glioblastoma. This meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII mutation are predictors of survival in patients with glioblastoma and anaplastic astrocytoma. MATERIALS AND METHODS: Medline, the Cochrane Central Register of Controlled Trials, EMBASE, and Google Scholar databases were searched until July 31, 2014. Studies were selected for inclusion in the analysis if they included patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII mutation status was reported, and overall survival (OS) data were reported. RESULTS: Of 113 articles initially identified, only eight contained data with respect to the outcome of interest and were included in the meta-analysis. The number of cases ranged from 14 to 268, and the majority of patients were 60 or more years of age. There was no significant difference in OS between EGFR amplification-positive and EGFR amplification-negative glioblastoma patients (pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P = 0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852, 2.482, P = 0.169). There was no significant difference in OS between EGFRvIII-positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI: 0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies, and the significance changed when the analysis was performed with studies removed in turn. CONCLUSIONS: There is insufficient evidence that either EGFR amplification or the EGFRvIII mutation has prognostic value in patients with glioblastoma.

Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs.

OBJECTIVE: The main objective of this study was to investigate, in a population of normal postmenopausal women, the association between menopause and severity of lumbar disc degeneration from the first lumbar to the first sacral vertebra on magnetic resonance imaging. METHODS: Between January 2010 and May 2013, 846 normal women and 4230 intervertebral discs were retrospectively analyzed. Age, height, weight and years since menopause (YSM) were recorded. Disc degeneration was evaluated using the modified Pfirrmann grading system. RESULTS: Compared to premenopausal and perimenopausal women, postmenopausal women had more severe disc degeneration after removal of age, height and weight effects (p < 0.0001). Postmenopausal women were divided into six subgroups for every 5 YSM. When YSM was below 15 years, there was a significant difference between every two groups, i.e. groups 1-5 YSM, 6-10 YSM and 11-15 YSM (p < 0.01). A positive trend was observed between YSM and severity of disc degeneration, respectively, i.e. L1/L2 (r = 0.235), L2/L3 (r = 0.161), L3/L4 (r = 0.173), L4/L5 (r = 0.146), L5/S1 (r = 0.137) and all lumbar discs (r = 0.259) (p < 0.05 or 0.01). However, when YSM was above 15, there was no difference, i.e. groups 16-20 YSM, 21-25 YSM and 26-30 YSM (p > 0.05), and the significance correlation also disappeared (p > 0.05). CONCLUSION: Menopause is associated with disc degeneration in the lumbar spine. The association almost entirely occurred in the first 15 years since menopause, suggesting estrogen decrease may be a risk factor for lumbar disc degeneration.

Cerebral hyperaemia after isoflurane anaesthesia for craniotomy of patients with supratentorial brain tumour.

BACKGROUND: Few studies look into cerebral blood flow (CBF) changes during emergence from general anaesthesia for craniotomy. The purpose of this study was to assess CBF changes during emergence from general anaesthesia for craniotomy, through monitoring blood oxygen saturation of jugular vein bulb (SjvO2 ) and transcranial Doppler (TCD). METHODS: We enrolled 30 patients undergoing selective craniotomy (group C) for supratentorial brain tumour resection and 30 patients undergoing selective abdominal surgery (group A). Mean velocity of middle cerebral artery (Vmca), mean arterial pressure (MAP), SjvO2 (only measured in group C), and arterial CO2 partial pressure were measured before anaesthesia, at tracheal extubation, and 30, 60, 90, 120 min after extubation. RESULTS: Vmca of the same side of tumour was significantly higher than contralateral Vmca before anaesthesia and at all times after extubation in group C. The ipsilateral Vmca increased significantly (95.7 ± 16.9 cm/s vs. 63.7 ± 6.7 cm/s, P < 0.01) at extubation in group C, then declined but still above baseline significantly in the first 2 h after extubation. While Vmca of the right side changed only slightly (63.6 ± 7.7 cm/s vs. 61.8 ± 8.1 cm/s, P < 0.01) but significantly at extubation in group A. SjvO2 increased significantly (81.4% ± 7.4% vs. 60.9% ± 3.7%, P < 0.01) at extubation in group C, and remained above baseline significantly for 2 h. There was no significant correlation between Vmca and MAP at any time. CONCLUSIONS: Cerebral hyperaemia occurs after supratentorial brain tumour resection surgery. The hyperaemia is more pronounced on the same side as the tumour.

Comparative gene expression profiling reveals key pathways in septic skeletal muscle.

AIM: Skeletal muscle transcriptome of patients with sepsis was compared with that of controls to elucidate the molecular mechanisms underlying sepsis-induced skeletal muscle dysfunction. MATERIALS AND METHODS: Gene expression data set GSE13205 was downloaded from Gene Expression Omnibus (GEO), including 13 septic samples and 8 controls. Differentially expressed genes (DEGs) were screened out with t-test. Transcriptional regulatory network was constructed for the DEGs with information from UCSU. In order to identify altered biological functions in sepsis, pathway enrichment analysis was conducted for all the genes in the network with DAVID. Besides, relevant small molecules were retrieved using the Connectivity Map (camp). RESULTS: A total of 287 DEGs were obtained in sepsis, 149 up-regulated and 138 down-regulated. A transcriptional regulatory network containing 83 nodes and 98 edges was then constructed. Five transcription factors (TFs) and their target genes were acquired. Significantly altered biological pathways included insulin signaling pathway, neurotrophin signaling pathway, fructose and mannose metabolism, circadian rhythm and apoptosis. Besides, a number of relevant molecules were obtained, such as trazodone and thapsigargin. CONCLUSIONS: Our study provided an insight into the molecular changes sepsis and related skeletal muscle dysfunction. The information could be beneficial in disclosing the pathogenesis and developing effective therapies.

Alcohol intake and the risk of chronic kidney disease: results from a systematic review and dose-response meta-analysis.

Many prospective cohort studies have investigated the association between the consumption of alcohol and CKD risk and have revealed inconsistent results. In the present study, we aimed to perform a meta-analysis of these studies to assess this association.We searched the PubMed and Embase databases up to 2020 and reviewed the reference lists of relevant articles to identify appropriate studies. We calculated the pooled relative risks with 95% CIs using random effects models, and then performed subgroup and meta-regression analyses. Dose-response meta-analyses were performed by sex separately. We identified 25 eligible prospective cohort studies, including 514,148 participants and 35,585 incident CKD cases. Compared with the category of minimal alcohol intake, light (RR = 0.90, I2 = 49%), moderate (RR = 0.86, I2 = 40%), and heavy (RR = 0.85, I2 = 51%) alcohol intake were associated with a lower risk of CKD. Subgroup meta-analysis by sex indicated that light (RR = 0.92, I2 = 0%), moderate (RR = 0.83, I2 = 39%) and heavy (RR = 0.76, I2 = 40%), alcohol consumption were inversely associated with CKD risk in male. Dose-response meta-analyses detected a nonlinear inverse association between alcohol consumption and the risk of CKD in all participants and linear inverse association in female participants. This meta-analysis shows that light (<12 g/day), moderate (12-24 g/day), and heavy (>24 g/day) alcohol consumption are protective against chronic kidney disease in adult participants especially in males.

Effects of disulfide bridges glycoprotein E1 on fusogenic activity of Rubella virus.

Rubella virus (RUBV) infects cells via an acid-triggered membrane fusion process. RUBV virions contain two cysteine-rich glycoproteins, E2 and E1. The latter is believed to be involved in the membrane fusion. Using a recombinant plasmid containing RUBV E1 and E2, 11 of total 20 cysteines present in the ectodomain of wild type E1 were mutated to test their role in the fusion via the formation of disulfide bridges. The recombinant plasmids containing mutated E1 (Cys2-Cys20) or wild type (wt) E1 were expressed in BHK-21 cells. Their fusogenic and hemadsorption activities in addition to a potential of cell surface expression of E1 and E2 were assayed. The results showed that the fusogenic activity was lost in all tested mutants, while the hemadsorption activity and cell surface expression potential were affected differently in individual mutants. Since only the Cys5 and Cys8 mutations led to a reduction of both hemadsorption and cell surface expression, we assume that these mutations prevented the formation of the disulfide bridge, what led to a misfolding of E1 and consequently to a failure of recognition of E1 by E2. In conclusion, the disulfide bridges disrupted in all the tested mutants appear essential for the cell fusion, while only the disulfide bridge C(5)-C(8) seems to be crucial for the transport of E1 and E2 in the cell.

Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells.

Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated protein which is localized in either the cell membrane or nucleus depending on its palmitoylated state. The increasing evidence showed the biological roles of PLSCR1 in cell signaling, maturation and apoptosis. To investigate the functions of PLSCR1 in leukemic cells, we generated an inducible PLSCR1-expressing cell line using myeloid leukemic U937 cells. In this cell line, PLSCR1 was tightly regulated and induced upon tetracycline withdrawal. Our results showed that inducible PLSCR1 expression arrested the proliferation of U937 cells at G1 phase. Meanwhile, PLSCR1-overexpressing U937 cells also underwent granulocyte-like differentiation with increased sensitivity to etoposide-induced apoptosis. Furthermore, we also found that PLSCR1 induction increased cyclin-dependent kinase inhibitors p27(Kip1) and p21(Cip1) proteins, together with downregulation of S phase kinase-associated protein 2 (SKP2), an F-box subunit of the ubiquitin-ligase complex that targets proteins for degradation. Additionally, PLSCR1 induction significantly decreased c-Myc protein and antiapoptotic Bcl-2 protein. Although the exact mechanism by which PLSCR1 regulates these cellular events and gene expression remains unresolved, our results suggest that PLSCR1 plays the antagonistic role regarding leukemia development. These data will shed new insights into understanding the biochemical and biological functions of PLSCR1 protein.

Gingival enlargement in a pregnant woman with acute monocytic leukaemia: a case report.

The objective of the present study was to report the case of a pregnant woman with severe gingival enlargement for 3 months with undiagnosed acute leukaemia. The pregnant woman presented with anaemia and generalized gingival enlargement. A provisional diagnosis of gingival enlargement in pregnancy was made. Twelve days after the initial treatment, the patient was referred and admitted to the haematology department of a local hospital with clinical signs of anaemia and thrombocytopenia. Blood count showed a white blood cell count of 9.68 × 109 /L, with a haemoglobin count of 64.0 g/L and a platelet count of 17 × 109 /L. Bone marrow aspiration showed 94.5% monoblasts, and the morphological diagnosis was acute monocytic leukaemia. One day after admission, the patient delivered a male infant by Caesarean section. Ten days after the Caesarean section, the patient was started on a course of chemotherapy. Pulmonary infection, hypokalaemia, and respiratory failure developed, and the patient died 23 days after the Caesarean section. The present case shows the importance of awareness of severe gingival enlargement as an initial oral sign of acute leukaemia.

A new design of internal fixation for scoliosis and its preliminary clinical application.

A new scoliotone composed of screw, socket, distraction rod, lateral mass and compression rod can produce free movement in three different planes and fix the vertebral column in three-dimensions. The instrument has a strong force of fixation, distraction, compression and anti-rotation and it can be locked in any degree angle. Preliminary clinical application in 10 cases showed that when the spinal curvature (Cobb's angle) was less than 50, the average correction rate of scoliosis was 78.2% and that of the hump was 90%; when Cobb's angle was within 50-100 degrees, the average curve correction was 68.2%, and the hump correction 87.7%; when Cobb's angle was 100 degrees, the average curve correction was 63.3%, and the hump correction 82%. The vertebral column needed no external fixation after the operation. Biomechanical characteristics of the vertebral pedicle, and the technical features are discussed.

Analysis of related factors on the deformity correction of balloon kyphoplasty.

BACKGROUND AND PURPOSE: Balloon kyphoplasty is a minimally invasive surgical approach for treating vertebral compression fractures, including osteoporotic vertebral compression fractures. The purpose of this study was to determine the effect of balloon inflation and postural reduction on balloon kyphoplasty for the deformity correction of vertebral compression fractures and to explore the correlative factors affecting the deformity correction. MATERIALS AND METHODS: A retrospective study of 72 patients (75 levels) who had undergone balloon kyphoplasty was conducted. Imaging data and clinical features were collected and analyzed. Independent-samples t test analysis was used to find the possible factors affecting deformity correction. RESULTS: Postural correction in the overextending position significantly increased anterior middle vertebral height, kyphotic angle, and Cobb angle (each P < .05). There was no significant difference in anterior, middle vertebral height, kyphotic angle, and Cobb angle between postural reduction and balloon dilation (each P > .05). The improvement on the Visual Analog Scale was notable (P < .05). Among a variety of factors, the fracture type (wedge type and biconcave type) affected both the height restoration (P = .003) and kyphotic angle reduction (P = .007). The bone cement injected volume was related to height restoration (P = .011) and kyphotic angle reduction (P = .018). CONCLUSIONS: Balloon inflation was useless for deformity correction. The deformity correction was attributed to postural reduction with cement strengthening. The most significant factors affecting deformity correction were the fracture type and bone cement injected volume.

A radiological and cadaveric study of oblique lumbar interbody fixation in patients with normal spinal anatomy.

The purpose of this study was to determine whether it would be feasible to use oblique lumbar interbody fixation for patients with degenerative lumbar disease who required a fusion but did not have a spondylolisthesis. A series of CT digital images from 60 patients with abdominal disease were reconstructed in three dimensions (3D) using Mimics v10.01: a digital cylinder was superimposed on the reconstructed image to simulate the position of an interbody screw. The optimal entry point of the screw and measurements of its trajectory were recorded. Next, 26 cadaveric specimens were subjected to oblique lumbar interbody fixation on the basis of the measurements derived from the imaging studies. These were then compared with measurements derived directly from the cadaveric vertebrae. Our study suggested that it is easy to insert the screws for L1/2, L2/3 and L3/4 fixation: there was no significant difference in measurements between those of the 3-D digital images and the cadaveric specimens. For L4/5 fixation, part of L5 inferior articular process had to be removed to achieve the optimal trajectory of the screw. For L5/S1 fixation, the screw heads were blocked by iliac bone: consequently, the interior oblique angle of the cadaveric specimens was less than that seen in the 3D digital images. We suggest that CT scans should be carried out pre-operatively if this procedure is to be adopted in clinical practice. This will assist in determining the feasibility of the procedure and will provide accurate information to assist introduction of the screws.

Association between perioperative glucose levels and adverse outcomes in infants receiving open-heart surgery with cardiopulmonary bypass for congenital heart disease.

There is no consensus that hyperglycaemia is an independent predictor of morbidity-mortality in children. This retrospective observational study aimed to assess the association between abnormal perioperative glucose levels and adverse outcomes in infants receiving open-heart surgery with cardiopulmonary bypass. The records of a total of 233 infants who underwent cardiopulmonary bypass for a variety of congenital cardiac procedures between January and December 2010 were reviewed. The blood glucose levels, demographic and perioperative information were recorded. Patients who experienced complications (n=91) were compared with those who did not (n=142). We found both intraoperative and postoperative glucose levels increased compared to the preoperative values (P<0.001). Thirty patients (12.8%) experienced hyperglycaemia and 15 patients (6.4%) experienced at least one episode of hypoglycaemia during surgery. Within the first two days after surgery, 12 (5.2%) patients experienced hyperglycaemia and 32 (13.7%) became hypoglycaemic in the paediatric intensive care unit. However, the abnormal perioperative glucose levels were not associated with increased adverse outcomes. After adjusting for other potential variables, lower weight at surgery, longer surgery time and hospital length-of-stay are the independent predictors of morbidity-mortality. Our findings suggest that perioperative hyperglycaemia and mild transient hypoglycaemia do not appear to be detrimental to infants with congenital heart disease, although we did not assess neurological outcomes. Nevertheless, due to the limitations of the retrospective design of this study and its limited power, more thorough clinical randomised controlled trials are needed.

Management of acute combination atlas-axis fractures with percutaneous triple anterior screw fixation in elderly patients.

INTRODUCTION: Patients with combined C1-2 fractures were often treated by posterior arthrodesis. However, elderly patients with multiple injuries (such as brain injury), the large surgical trauma of posterior arthrodesis will increase the risk of perioperative mortality. A minimally invasive technique may be better for them, and decrease the risk of perioperative mortality. MATERIALS AND METHODS: Seven patients with combined C1-2 fractures underwent percutaneous anterior odontoid screw and anterior C1-2 transarticular screws (percutaneous triple anterior screws fixation). The surgical technique of percutaneous triple anterior screws fixation is described. RESULTS: The operation performed on all patients successfully without technical difficulties, and no intra-operative surgery-related complications such as vertebral artery, nerve injury and soft tissue complications occurred. No pullout, loosening, or breakage of internal screws was observed. C1/2 stable was found in all cases and radiographic union achieved in all odontoid fractures. CONCLUSION: Using the appropriate instruments allied to intra-operative image-intensification, we suggest that percutaneous triple anterior screw fixation is reliable, effective and minimally invasive procedure for elderly and brain injured patients suffering of combined atlas-axis fractures. LEVEL OF EVIDENCE: Level IV. Retrospective study.

Percutaneous anterior transarticular screw fixation for atlantoaxial instability: a case series.

We reviewed the outcome of a retrospective case series of eight patients with atlantoaxial instability who had been treated by percutaneous anterior transarticular screw fixation and grafting under image-intensifier guidance between December 2005 and June 2008. The mean follow-up was 19 months (8 to 27). All eight patients had a solid C1-2 fusion. There were no breakages or displacement of screws. All the patients with pre-operative neck pain had immediate relief from their symptoms or considerable improvement. There were no major complications. Our preliminary clinical results suggest that percutaneous anterior transarticulation screw fixation is technically feasible, safe, useful and minimally invasive when using the appropriate instruments allied to intra-operative image intensification, and by selecting the correct puncture point, angle and depth of insertion.