Recently, with the development of techniques such as proteomics, the positive rate of com-mon tumor markers, such as carcinoembryonic antigen (CEA) and squamous cell carcinomatous antigen (Scc-Ag) has increased obviously. And some new tumor markers related to esophageal carcinoma (EC) have been detected, such as vascular endothelial growth factor, angiopoietin, Dickkopf21, tumor M2-PK and etc. Clinical trials are undergoing to estimate the value of these markers,which may change the current status of EC diagnosis and therapy.

Objective To explore the expression of DKK-1 and its clinical value in patients with e-sophageal cancer. Methods The levels of serum DKK-1 were measured by sandwich enzyme linked immu-nosorbent assay(ELISA) in 80 patients with esophageal squamous cell cancer and in 35 healthy subjects. The sensitivities of serum DKK-1, CEA and CYFRA21-1 in the patients with esophageal squamous cell cancer were calculated and analyzed to compare their values in diagnosis of esophageal cancer. Results The serum DKK- 1 levels in patients with esophageal squamous cell cancer were significantly higher than those of healthy subjects(P<0.05). According to the highest value of medicine reference of DKK- 1 (14. 54 ng/ml), its sensitivity and specificity were 66. 25% and 82. 86% respectively; There was a significant difference between the sensitivity of DKK-1 in patients with esophageal squamons cell cancer(66. 25%) and that in healthy subjects(17.14%) (P<0.05). The sensitivitis of serum DKK- 1 in patients with esophageal squamous cell cancer were associated with tumor size, TNM stage and lymph node metastasis(P <0.05),but not associated with gender,age and differentiation grade(P>0.05). And the sensitivity of DKK-1 (66. 25%) was significantly higher than that of CEA, CYFRA21-1 (39. 44% ,25. 35%, P <0. 01). Conclusion DKK-1 played a very important role in the growth and metastasis of esophageal cancer and may be a new tumor marker or an important index in the diagno-sis of esophageal cancer.

OBJECTIVE: To evaluate the clinical value of lidocain in the treatment of tinnitus through three routes of administration (intravenous, intratympanic and acupoint injection) by analyzing literatures. METHOD: Articles were collected through Hownet, Wanfang, VIP, Pubmed, SciVerse ScienceDirect, Springer and OVID, etc. The articles were strictly evaluated based on their quality. The Meta-analysis was performed to evaluate the outcomes by RevMan 5. 2 software. RESULT: A total of 16 articles with 1203 patients were enrolled in the analysis. Their tinnitus history ranged from 7 hours to 20 years. Assessment methods include tinnitus loudness levels, severity scales and subjective feelings. None of articles refer to maintaining time, instead of "short-term", "short" and so on. A total of 133 cases received intravenous injection and the effective rate was 73.4% (98 cases). 50 cases and 332 cases received intratympanic and acupoint injection respectively and their effective rates were 74.0% and 87.7%, respectively. The effective rate ranged from 42.4% to 58.3% in control group. Meta-analysis results indicate that all three routes of lidocaine administrations are more effective than conventional methods (P < 0.05). CONCLUSION Different routes of lidocaine administration have a good but short time effects on the tinnitus control. It can effectively reduce the time of tinnitus habituation as a complementary treatment. But its value still needs further evaluation.
Humans ; Lidocaine ; administration & dosage ; therapeutic use ; Tinnitus ; drug therapy

Recurrent intracerebral hemorrhage is a very serious cerebrovascular disease.Its incidence has shown a clear upward trend, and both disability and mortality have increased significantly compared to the first intracerebral hemorrhage. This article reviews the clinical classification, characteristics, risk factors, pathogenesis, and prognosis of recurrent intracerebral hemorrhage.

Moyamoya disease is a chronic progressive cerebrovascular disease. Its disability rate and lethality rate are higher. The direct and indirect revascularization can increase cerebral blood flow and reduce the occurrence of cerebral ischemia and cerebral hemorrhage. This article reviews the pathophysiological basis of its surgical treatment, surgical timing, indications, surgical treatment methods and efficacy.

OBJECTIVETo explore the molecular etiology for a Chinese family affected with isolated methylmalonic acidemia (MMA).

METHODSPotential mutations of MUT, MMAA and MMAB genes in the proband were screened by PCR and Sanger sequencing. The pathogenicity of identified mutations was analyzed using Polyphen2, SIFT, HSF, DNAMAN 6.0 and Swiss-PdbViewer4.1.0 software.

RESULTSTwo novel mutations of the MUT gene, including c.581C>T (p.P194L) and c.1219A>T (p.N407Y), were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that both mutations were damaging. The affected codons P194 and N407, both located in the (beta, alpha) 8 barrel domain and to which the substrate methylmalonyl-CoA is bound, are highly conserved across various species. Both mutations can disrupt the space conformation of its protein product, affecting the function of the MCM protein.

CONCLUSIONThe novel mutations of MUT gene probably underlie the isolated MMA in this family.

Adult ; Amino Acid Metabolism, Inborn Errors ; enzymology ; genetics ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Humans ; Infant ; Male ; Methylmalonyl-CoA Mutase ; genetics ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Point Mutation ; Sequence Alignment

OBJECTIVETo explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.

METHODSPCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes. SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species. Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.

RESULTSFor the proband, a compound heterozygous mutation was discovered in the MCCC1 gene, namely c.539G>T (p.G180V) and c.704_711del (p.A235Vfs*4), which were inherited from his father and mother, respectively. The two mutations have disrupted the protein conformation, which in turn may impact the function of MCC protein.

CONCLUSIONThe compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.

Amino Acid Sequence ; Base Sequence ; Carbon-Carbon Ligases ; chemistry ; deficiency ; genetics ; DNA Mutational Analysis ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Models, Molecular ; Mutation ; Neonatal Screening ; methods ; Protein Conformation ; Sequence Homology, Amino Acid ; Urea Cycle Disorders, Inborn ; diagnosis ; genetics

Objective To analyze the prognostic influencing factors of pulmonary adenocarcinoma with a micropapillary pattern (MPPAC).Methods A total of 109 MPPAC patients who received surgical operation in Shandong Cancer Hospital Affiliated to Shandong University from August 2012 to August 2015 were retrospectively analyzed.The median survival time and the survival rate of 1-,3-and 5-year were calculated by using Kaplan-Meier method,log-rank test was used for single-factor analysis and Cox regression analysis was used for multiple-factor analysis.Results The median overall survival time of 109 MPPAC patients was 55.0 months (3-67 months).The overall survival rate of 1-,3-and 5-year was 89.0％,61.5％,48.6％,respectively.Single factor analysis showed that the gender (x2 =7.208,P =0.007),the tumor size (x2 =24.083,P ＜ 0.01),lymph node metastasis (x2 =23.068,P ＜ 0.01),vascular tumor thrombosis (x2 =16.411,P ＜ 0.01),visceral pleural infiltration (x2 =18.438,P ＜ 0.01) and multiple tumors (x2 =28.563,P ＜0.01) were associated with the overall survival of MPPAC patients.Multiple factor analysis showed that the tumor size (RR =1.629,95％ CI 1.145-2.317,P =0.007),lymph node metastasis (RR =1.680,95％ CI 1.161-2.430,P =0.006) and vascular tumor thrombosis (RR =2.867,95％ CI 1.286-6.392,P =0.010) were the independent prognosis factors for MPPAC patients.Conclusion The MPPAC patients have a poor prognosis.The tumor size,lymph node metastasis and vascular tumor thrombosis could influence the prognosis of MPPAC patients.

Objective: To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases. Methods: Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases. Results: Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype. Conclusion The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

Objective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty－seven children diagnosed as PKU in the Maternal and Children＇s Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty－seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68／74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G＞A (p. R408Q),c. 728G＞A(p. R243Q)and c. 721C＞T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C＞ T(p. T105I),c. 583A＞ G(p. K195E),c . 851G＞A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.