[Efficacy of one-stage total spondylectomy and circumferential reconstruction for axial tumors through a combined anterior retropharyngeal-posterior approach].

Objective: To elucidate the safety and efficacy of one-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach for axial tumors. Methods: A total of 20 patients with axial tumor who received total spondylectomy through a combined anterior retropharyngeal-posterior approach in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from February 2006 to December 2018 were retrospectively analyzed. Anterior reconstruction was performed with a special-shaped titanium mesh or three-dimensional printed (3DP) implants. The degree of local pain and neurological function was assessed by the visual analogue scale (VAS) and Frankel classification systems, respectively. Status of internal fixation and local recurrence was analyzed by radiological examination during follow-up. Results: Among the 20 patients, 12 were male and 8 were female with a mean age of (59.1±11.0) years (31 to 72 years). The mean operation time was (605.0±60.1) minutes (430 to 700 minutes) with a mean intraoperative blood loss of (1 250±347) ml (800 to 2 400 ml). The mean postoperative hospital stay was (13.2±2.8) days (8 to 20 days), and mean follow-up duration was (37.2±14.2) months(14 to 66 months). Anterior reconstructions were performed with a special-shaped titanium mesh in 14 patients and with 3DP implants in another 6 patients. Posterior occipital-cervical fixation was performed in 5 patients, while cervical fixation only in another 15 patients. The mean VAS score of pain at the last follow-up decreased significantly when compared with that before operation (1.6±0.6 vs 7.1±1.1, P<0.001). Nine patients with neurological deficits indicated significant improvement by at least 1 level at the last follow-up; among them, 2 cases of Frankel B improved to Frankel C and D, respectively; 3 cases of Frankel C all improved to Frankel D, and 4 cases of Frankel D improved to Frankel E. The perioperative complications included: 2 cases of vertebral artery injury, 2 cases of dysphagia, 3 cases of hoarseness and cough, 2 cases of cerebrospinal fluid leakage, and 1 case of greater occipital neuralgia. At the last follow-up, 5 patients died and 3 patients relapsed. Only 1 case suffered fixation failure due to local recurrence at the last follow up. Conclusions: One-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach is safe and effective for axial tumors with favorable clinical outcomes and minor complications. Circumferential reconstruction with special-shaped titanium mesh or 3DP implant and posterior fixation can effectively reconstruct mechanical stability.

[A novel mutation of SCN4A gene causes hypokalemic periodic paralysis in a Chinese family].

Objective: To report a Chinese family with hypokalemic periodic paralysis (HOKPP) and investigate the clinical and pathogenic gene characteristics of the family. Methods: The clinical, electrophysiological and pathological data of the proband of the family were analyzed, and the information of the family was investigated in detail. The peripheral venous blood of the six members of the family was collected and their genomic DNA was extracted. The genes related to periodic paralysis analysis of the proband were performed by the second generation sequencing. The pathogenicity of the mutant protein was respectively analyzed by the bioinformatics software SIFT, Polyphen2 and Mutation Tasker. The cosegregation analysis of phenotype and genotype of the family was performed by the first generation sequencing. Results: There were 3 patients in the family with the onset age of 21 to 42 years old. All the patients manifested with vomiting as the first symptoms, then presented with muscle weakness accompanied by muscle soreness. The muscle weakness gradually relieved in 3 to 5 days. Creatine kinase (CK) of the proband significantly increased. Electromyographic exercise test was positive, however, electromyography and muscle pathological analysis were normal. The genes related to periodic paralysis analysis of the proband found a novel mutation (c.2458A>T (p.N.820Y)) of SCN4A gene which was located in the conservative region. The function analysis showed it was a pathogenic mutation. Moreover, the first generation sequencing confirmed that the mutation was cosegregated with patients in the family. Meanwhile, it was found that the proband's son carried the same mutation, but without any symptom, indicating that he was a pre-symptomatic patient. Conclusions: Vomiting can be one of the symptoms of the patients with HOKPP. The novel mutation of SCN4A gene c.2458 A>T is the pathogenic mutation of the family. Patients with periodic paralysis should be tested for blood potassium and genes as early as possible to facilitate early diagnosis and genetic counseling.

[Acute kidney injury diagnosed by elevated serum creatinine increases mortality in ICU patients following non-cardiac surgery].

Objective: To analyze whether acute kidney injury (AKI) patients diagnosed by elevated serum creatinine had a higher risk of in-hospital mortality following non-cardiac surgery compared with those diagnosed by oliguria alone according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods: This was a secondary analysis of a previous retrospective cohort study. A total of 729 consecutive adult patients with high risk of AKI admitted to the intensive care unit (ICU) of Peking University First Hospital after non-cardiac surgery were enrolled in the previous study from July 2017 to June 2018. Postoperative AKI patients were diagnosed and categorized according to KDIGO criteria. In this secondary analysis, all patients with AKI were selected. Patients diagnosed by elevated serum creatinine were enrolled into the AKI-Scr group, while those with oliguria alone were included in the AKI-UO group. A multivariable logistic regression model was established to assess the relationship between elevated serum creatinine and in-hospital mortality in AKI patients. Results: Of 188 AKI patients [(71±14) years, 114 males (60.6%)], 72 (38.3%) and 116 (61.7%) patients were enrolled in AKI-Scr and AKI-UO group, respectively. The rate of in-hospital mortality was 16.7% in AKI-Scr group, which was significantly higher than that in AKI-UO group (0.9%, P<0.001). Furthermore, patients in AKI-Scr group had longer postoperative hospital and ICU stay, more duration of mechanical ventilation and higher total medical costs (all P<0.05). Multivariate logistic regression analysis revealed that AKI-Scr (OR=20.286, 95%CI: 2.544-161.797, P=0.004) and preoperative hypoproteinemia (OR=4.897, 95%CI: 1.240-19.329, P=0.023) were independent risk factors for in-hospital mortality in postoperative AKI patients. Conclusions: AKI patients diagnosed by increased serum creatinine had a higher risk of in-hospital mortality following non-cardiac surgery, accompanied by several worsen short-term outcomes and higher total medical costs, compared with those diagnosed by oliguria alone according to the KDIGO criteria. More attention should be paid to AKI patients diagnosed by elevated serum creatinine, to improve the prognosis.

[Clinical and radiographic evaluation of oblique lumbar interbody fusion combined with posterior surgery via Wiltse approach for adult degenerative scoliosis].

Objective: To assess the clinical effect of oblique lumbar interbody fusion (OLIF) combined with posterior surgery via Wiltse approach for adult degenerative scoliosis. Methods: The clinical data of 27 patients with adult degenerative scoliosis who received OLIF operation from April 2015 to June 2018 in Tongji Hospital were analyzed retrospectively. There were 17 males and 10 females with an average age of (54±11) years. All patients were treated with OLIF combined with pedicle screw fixation via Wiltse approach. Operation time, blood loss and surgery complications were all recorded. Clinical and radiographic evaluation were investigated at 1 week, 3 months of post operation and final follow-up. Visual analog scale (VAS) for low back pain and leg pain, Oswestry disability index (ODI) for low back pain were used to evaluate the clinical efficacy of surgery. Lumbar coronal cobb angle, lumbar lordosis (LL), pelvic tilt (PT), mismatch of PI and PT, sagittal vertical axis (SVA) were investigated with full spine standing X-ray. The data were compared with factor analysis of variance. Results: All patients were followed-up for 6-52 months ((30±5) months). The operation time was (235±33) min, the blood loss was (433±62) ml. VAS for low back pain and eg pain and the ODI were significantly improved from 6.8±1.4, 7.3±1.4 and 71%±11% preoperatively to 1.1±1.2, 1.0±0.9 and 17%±6% at the latest follow-up (F=115.302,139.855,291.198, all P<0.05).Lumbar coronal Cobb angle of patients was reduced from 28°±8° preoperatively to 9°±4° at the latest follow-up (F=66.352, P<0.05). The LL was significantly increased from 20°±11° preoperatively to 33°±7° (F=17.678, P<0.05), and PT, PI-LL and SVA were significantly increased from 31°±6°,35°±12° and (90±29) mm preoperatively to 26°±5°, 21°±6° and (32±17) mm at the latest follow-up (F=6.211,23.809,53.372, all P<0.05). There was no severe vascular andnerve injuries during and after operation. Conclusion: OLIF combined with posterior surgery via Wiltse approach is a safe and effective operation in the treatment of adult degenerative scoliosis with mild to moderate sagittal imbalance, it can correct the coronal and sagittal deformity, and achieve less surgery injury, less complications and good clinical results.

LncRNA SNHG4 promotes neuroblastoma proliferation, migration, and invasion by sponging miR-377-3p.

Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.

MiRNA-206 inhibits proliferation of renal clear cell carcinoma by targeting ZEB2.

OBJECTIVE: The purpose of this study was to investigate the effect of microRNA-206 on the malignant progression of renal clear cell carcinoma (RCC). In addition, whether microRNA-206 could regulate ZEB2 expression and the underlying mechanisms was also explored. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-206 level in 46 tumor tissue specimens and adjacent ones of RCC patients. Also, the relationship between microRNA-206 expression and clinical indicators of RCC was analyzed. The negative control (NC) and microRNA-206 mimics were transfected into RCC cell lines, and the transfection efficiency was verified by qRT-PCR. The effects of microRNA-206 on the proliferation and apoptosis of RCC cells were analyzed by cell counting kit-8 (CCK-8), clone formation, and flow cytometry assays. Finally, the regulation of microRNA-206 on the downstream gene ZEB2 was indicated by Western Blot and cell recovery experiments. RESULTS: qRT-PCR results showed that the expression level of microRNA-206 in tumor tissue samples of RCC patients was remarkably lower than that in adjacent normal tissues, and the difference was statistically significant. Meanwhile, compared with patients with high expression of microRNA-206, the pathological stage of patients with low expression of microRNA-206 was higher, and the overall survival rate was lower. In the RCC cell lines (Caki-1 and Caki-2), the cell proliferation ability of the microRNA-206 overexpression group was remarkably weakened, while the cell apoptosis rate was oppositely enhanced when compared with the NC group. In addition, this study demonstrated that ZEB2 expression was remarkably increased in RCC cells as well as tissues and was negatively correlated with microRNA-206 expression. At the same time, microRNA-206 mimics was found remarkably reduced in the expression of proteins in ZEB2-related signaling pathway, including ZEB2, ß-catenin, cyclinD1, c-Myc, MMP-2, and MMP-9. In the cell reverse experiment, the overexpression of ZEB2 was found to be able to counteract the impact of microRNA-206 mimics on RCC cell proliferation and apoptosis and thus, participated in the malignant progression of RCC. CONCLUSIONS: This study revealed that microRNA-206 was remarkably associated with the pathological stage and poor prognosis of RCC patients. In addition, microRNA-206 might inhibit the malignant progression of RCC by regulating the targeted ZEB2.

[Clinical phenotypes of hepatocyte nuclear factor 1 homeobox b-associated disease].

Objective: Hepatocyte nuclear factor 1 homeobox b (HNF1B) -associated disease is an autosomal dominant inherited disorder with a variable, multi-systemic phenotype. In China, five adult probands and one child proband with HNF1B-associated disease had been reported, whereas few fetuses are described. The aims of this retrospective study were to understand about the clinical manifestations of HNF1B-associated disease and to further improve the recognition of this disorder. Method: Four patients (3 males, 1 female) and three fetuses with HNF1B mutations were included in this study. They were admitted to our hospital from January 2013 to March 2017. HNF1B mutations were detected using targeted next generation sequencing and quantitative real-time PCR or Sanger sequencing. HNF1B heterozygous deletion of exons 1-9 was found in 4 patients and 2 fetuses, and HNF1B heterozygous missense mutation in 1 fetus. These two mutations had been reported. Two patients and 1 fetus had de novo mutations. Results of renal ultrasonography with or without magnetic resonance imaging, biochemical investigations, urine routine examination and other necessary investigations in 7 cases were analyzed. Result: Three patients were Han Chinese ethnicity, and one patient was Mongolian. In patients 1 and 4, abnormal fetal kidneys were discovered by routine ultrasonography, and the age at first feature identified in Patients 2 and 3 were 13 years and 28 years. Patient 3 had normal renal function and the remainder had reduced glomerular filtration rate. In addition, patient 4 presented with nephrotic syndrome and glycosuria, patient 2 with early onset hyperparathyroidism and renal osteodystrophy, and patient 3 with diabetes mellitus. All the 4 patients had renal structural abnormalities including bilateral multiple renal cysts, dysplasia and hyperechogenic kidneys. Only patient 3 had a positive family history of renal diseases, the remainder had a negative family history of renal diseases. In 3 fetuses, prenatal ultrasound anomalies were detected during the second trimester. These 3 fetuses had hyperechogenic kidneys with or without renal cysts. Polyhydramnios was detected in only one of the 3 fetuses. Two of the 3 fetuses had a positive family history of renal diseases. Conclusion: Clinical phenotypes of HNF1B-related disease are heterogeneous, renal malformations clearly appear to be the most common manifestation, multiple renal cysts are characteristic, and patients can progress to impaired kidney function during childhood; HNF1B mutation is a differential diagnosis of fetal hyperechogenic kidneys or multiple renal cysts.

[Effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis].

Objective: To study the effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis(AR).Method:Selected 97 cases diagnosed as moderate to severe persistent AR patients, were treated with specific immunotherapy for one year. All patients received the evaluation with symptom check list 90(SCL-90) and rhinoconjunctivitis quality of life questionnaire(RQLQ) before specific immunotherapy, six, and 12 months after specific immunotherapy.Result:The total scores, scores of somatization, obsessive, anxiety, depression and phobia in SCL-90 of AR patients after 12 months treatment were significantly lower than that before treatment（P < 0.05）. Total score of quality of life and subitem score in RQLQ of AR patients after 12 months treatment were obviously lower than that before treatment (P < 0.05）.Conclusion:Specific immunotherapy can effectively alleviate the clinical symptoms and improve psychological health level and quality of life of AR patients.

Meta-analysis: erythromycin before endoscopy for acute upper gastrointestinal bleeding.

BACKGROUND: Studies evaluating the effect of erythromycin on patients with acute upper gastrointestinal bleeding (UGIB) had been reported, but the results were inconclusive. AIMS: To compare erythromycin with control in patients with acute UGIB by performing a meta-analysis. METHODS: Electronic databases including PubMed, EMBASE and the Cochrane Library, Science Citation Index, were searched to find relevant randomised controlled trials (RCTs). Two reviewers independently identified relevant trials evaluating the effect of erythromycin on patients with acute UGIB. Outcome measures were the incidence of empty stomach, need for second endoscopy, blood transfusion, length of hospital stay, endoscopic procedure time and mortality. RESULTS: Four RCTs including 335 patients were identified. Meta-analysis demonstrated the incidence of empty stomach was significantly increased in patients receiving erythromycin (active group 69%, control group 37%, P<0.00001). The need for second endoscopy, amount of blood transfusion and the length of hospital stay were also significantly reduced (all P<0.05). A trend for shorter endoscopic procedure time and decreased mortality rate was observed. CONCLUSIONS: Prophylactic erythromycin is useful for patients with upper gastrointestinal bleeding to decrease the amount of blood in the stomach and reduce the need for second endoscopy, amount of blood transfusion. It may shorten the length of hospital stay, but its effects on mortality need further larger trials to be confirmed.

The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells.

The c-Jun NH2-terminal kinase (JNK) pathway represents one subgroup of MAP kinases that are activated primarily by cytokines and exposure to environmental stress. Autophagy is a protein-degradation system characterized by the formation of double-membrane vacuoles termed autophagosomes. Autophagy-related gene beclin 1 plays a key role in autophagosome formation. However, the relationships between activation of JNK pathway, autophagy induction and Beclin 1 expression remain elusive. In this study, we used human cancer cell lines CNE2 and Hep3B to investigate the role of JNK-mediated Beclin 1 expression in ceramide-induced autophagic cell death. Ceramide-treated cells exhibited the characteristics of autophagy (that is, acidic vesicular organelle formation and the LC3-II generation). JNK was activated in these two cell lines exposed to ceramide and the phosphorylation of c-Jun also increased. In the meantime, we found that ceramide upregulated Beclin 1 expression in cancer cells. The upregulation of Beclin 1 expression could be blocked by SP600125 (a specific inhibitor of JNK) or a small interfering RNA (siRNA) directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase reporter analysis revealed that c-Jun was involved in the regulation of beclin 1 transcription in response to ceramide treatment. In addition, inhibition of JNK activity by SP600125 could inhibit autophagy induction by ceramide. Furthermore, Beclin 1 knockdown by siRNA also inhibited ceramide-mediated autophagic cell death. JNK-mediated Beclin 1 expression was also observed in topotecan-induced autophagy. These data suggest that activation of JNK pathway can mediate Beclin 1 expression, which plays a key role in autophagic cell death in cancer cells.

Culture and growth characteristics of chondrocytes encapsulated in alginate beads.

Methodology is described for the culture of avian and mammalian chondrocytes in ionotrophically gelled "semi-solid" and "hollow" alginate beads. Chondrocytes grown in "semi-solid" gels exhibited a spherical shape as opposed to a fibroblastic morphology observed in monolayer culture. In the "semi-solid" beads, the cells grew as small clumps and as large aggregates. The aggregates were round or elliptical in appearance and surrounded by a dense Alcian Blue positive halo. Preliminary studies with collagen and chitosan matrixes encapsulated in "hollow" beads suggest that cell growth and morphology are profoundly influenced by the composition of the cellular environment. Chondrocyte structure and function in the "semi-solid" and "hollow" beads were partially characterized by light microscopy, histochemical and biochemical means. The encapsulation methodology is readily applicable for the culture of chondrocytes in single beads, in multiwell dishes, or mass culture.