Objective:To investigate clinical and dermoscopic manifestations of nail damage secondary to hand, foot and mouth disease.Methods:Clinical data were collected from 12 patients with nail damage secondary to hand, foot and mouth disease in Department of Dermatology, Shandong Provincial Hospital from June to November 2015, and characteristics of nail damage were analyzed.Results:The clinical manifestations of nail damage following hand, foot and mouth disease included dryness of periungual skin (12 cases) , nail plate cavities (11 cases) , nail fractures (11cases) and Beau′s lines (4 cases) . Dermoscopy showed nail discoloration (12 cases) , nail delamination (12 cases) , horizontal streaks (10 cases) , longitudinal streaks (8 cases) , brown background of the nail matrix (11 cases) , telangiectasia (7 cases) , periungual desquamation (12 cases) and red background (10 cases) .Conclusion:The clinical manifestations of nail damage following hand, foot and mouth disease are mainly dryness of periungual skin, nail plate cavities and fractures, and its dermoscopic manifestations include nail discoloration, delamination, horizontal and longitudinal streaks, brown background of the nail matrix, telangiectasia, periungual desquamation and red background.

RNA interference (RNAi), as a new technology of gene therapy, has been used in the studies of many diseases in vitro, however, targeting delivery of small interference RNA (siRNA) is still a bottleneck for clinical therapy of siRNA agents. Aptamer is a group of oligonucleotides with high affinity and targeting, and is becoming another important means of delivery for siRNA. In this review, we summarized siRNA delivery obstacles in vivo and recent attractive developments increatively using cell-internalizing aptamers to deliver siRNAs to target cells.

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.

Objective To study the rule of lower-cervical lymphatic metastasis in thoracic esophageal carcinoma,and make evaluation about the reasonable extent of lymphadenectomy. Methods One hundred and eight cases of thoracic esophageal carcinoma through chromatic ultrasound and CT before operation were divided into different groups selectively,while three fields lymphadenectomy (3-FL) was adopted in 31 cases,and two fields lymphadenctomy (2-FL) was adopted in 77 cases. Results The rate of lower-cervical lymphatic metastasis was 87.1%(27/31) through chromatic ultrasound and CT,and that was 25.0%(27/108) before the two up-mentioned examinations (P<0.05). In all cases, the rate of lower-cervical lymphatic metastasis in the upper pectoral esophageal carcinoma was 47.6% (10/21),that in the middle pectoral esophageal carcinoma was 21.3%(13161),and that in the middle and lower pectoral esophageal carcinoma was 19.5%(17187) ,P<0.05. Through 3-FL, the rate of lower--cervical lymphatic metastasis in the upper pectoral esophageal eareinoma was 57.1%(12/21), that in the middle pectoral esophageal carcinoma was 23.0%(14/61), and that in the middle and lower pectoral esophageal carcinoma was 21.8%(19/87), P<0.05. Conclusions The regionality metastasis is the main fashion in thoracic esophageal carcinoma with lower-cervical lymphatic metastasis. It is feasible to judge lower-cervical lymphatic metastasis through chromatic ultrasound and CT before operation.The 3-FL of the upper pectoral esophageal carcinoma is recommended. The 3-FL is selectable in the middle and lower pectoral esophageal carcinoma according to the result of chromatic ultrasound and CT.

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BACKGROUND:Uric acid as an endogenous antioxidant has garnered increasing attentions because of its anti-oxidation, anti-DNA damage and neuroprotective effects.
OBJECTIVE:To observe the effect of uric acid at different concentrations on the neural differentiation of bone marrow mesenchymal stem cells.
METHODS:Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro. The morphology change was observed. The third passages of bone marrow mesenchymal stem cells were induced to differentiate to neuron-like cells by induced liquid containing four different concentrations of uric acid (0 mmol/L as control group, 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L) for 24 hours. Then, after second intervention for 1 hour, cells were detected by Nissl staining and specific markers were detected by immunohistochemistry method.
RESULTS AND CONCLUSION:After induction, the cellbody shrank, forming processes and connections. Nissl body was found in the cytoplasm. The positive rates of neuron-specific enolase were significantly higher in uric acid groups of different concentrations compared to the control group (P<0.05);moreover, the positive rates of neuron-specific enolase were increased as the increase in concentrations of uric acid (P<0.05). The positive rates of Nestin were decreased in uric acid groups of different concentrations compared to the control group (P<0.05). After 4 hours of induction, cells fel off significantly. In a certain period of time, uric acid can promote differentiation of bone marrow mesenchymal stem cells into neuron-like cells in a certain concentration-dependent manner in vitro.

To study the effect of antioxidants R-(+)-lipoic acid (R-LA) on cells growth,proliferation and related mechanisms in human HepG2 cells lines.MTT was used to measure cells growth and proliferation.Reactive oxygen species (ROS) kit was used to analyze ROS level.Cell apoptosis and cell morphological changes were observed by flow cytometry and Hoechst 33258 test.Protein expression levels of apoptosis,autophagy and related pathway were analyzed through Western blot,including Bax,Bcl-2,caspase 3,PARP,ATG5,ATG7,LC3,Beclin1,mTOR,P70S6K,P38,P53,ERK and Akt etc.Results showed that cell growth and proliferation were inhibited in a dose-and time-dependent manner after being treated by lipoic acid.R-LA could increase ROS production,pro-apoptosis proteins Bax levels,activated caspase family and PARP.Meanwhile,R-LA could up-regulate the levels of autophagy-related proteins including ATG5,ATG7,Beclin1 and LC3,and down-regulate phosphomTOR and P70S6K levels.Signal pathway results showed that R-LA could up-regulate phospho-P38 and phospho-JNK levels,and decrease phospho-Akt and phospho-ERK.When adding 3-methyladenine,autophagy was inhibited.Thus,R-LA might activate autophagy and induce apoptosis by P38/AMPK-JNK,PI3K/AKT and Ras/ Raf/MEK/ERK pathways.

Objective To discuss the ultrasonographic characteristics of schistosomal appendicitis lesions. Methods Among the patients with schistosomal hepatopathy who were discovered by Color Doppler ultrasound in Huzhou Central Hospital from January 2012 to December 2015,50 cases with clear history of schistosomiasis and treatment were chosen as a schistosom?al hepatopathy group,meanwhile,50 normal people,who came from non?endemic areas,without schistosomal hepatopathy and schistosomiasis history were chosen as a control group. The two groups were examined by ultrasound scan of the appendix ,and the data of the largest diameter of the appendix and the thickness of the appendix wall were collected,and the sonographic char?acteristics of their appendixes,such as whether the echo of the appendix wall was even or not,were observed. Results The minimum internal diameter of the appendix cavity and the thickness of the appendix wall of the schistosomal hepatopathy group were(2.090 ± 0.790)mm and(1.332 ± 0.313)mm ,respectively,the former was significantly narrower than that of the control group,while the latter was significantly thicker than that of the control group(t=2.647,-4.526,respectively,both P<0.05). The proportions of those with inhomogeneous echo,indistinctness structure,uneven thickening of the appendix wall,as well as having intestinal contents in the appendix cavity in the schistosomal hepatopathy group were higher than those in the control group(χ2=12.000,18.537,24.008,4.244,respectively,all P<0.05). Conclusions Schistosomal appendicitis lesions have obvious ultrasonographic characteristics under ultrasound. Ultrasound can play an important role in judging whether the appen?dix of schistosomiasis patients is involved and discovering the lesion of appendix early.

Objective To prepare a redox-responsive doxorubicin-loaded nanoparticle,and to study its in vitro realease behavior and targeting effect on heptoma cells.Methods Cystamine was grafted on the side chains of hyaluronic acid with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide catalyst,and then β-cyclodextrin (β-CD) was conjugated on the amine groups of the cystamine by Schiff's base reaction to prepare β-CD modified hyaluronic acid (HACD).The HACD/DOX nanoparticles were prepared by encapsulating DOX into HACD using dialysis method.The drug loading,encapsulation efficiency,particle size and distribution,zeta potential and other physical and chemical properties,as well as in vitro drug release behavior of the HACD/DOX nanoparticles were characterized.The cytotoxicity of HACD/DOX nanoparticles to HepG2 cells was studied by cell counting kit-8 (CCK-8) method.The targeting effect of HACD/DOX nanoparticles on HepG2 cells was studied using flow cytometry and confocal laser scanning microscopy (CLSM).Results HACD were successfully synthesized,which could carry DOX to form uniform homogeneous nanoparticles.The drug loading of DOX in the nanoparticles was (16.1±0.2)％ and the encapsulation efficiency was (64.2±0.9)％.The transmission electron microscope images indicated that the shape of the HACD/DOX nanoparticles was homogeneous sphere.The results of granularity analysis showed that the average size of the HACD/DOX nanoparticles was (203.1 ±2.5) nm with a narrow size distribution (PDI =0.202).The zeta potential of the HACD/DOX nanoparticles was (-29.1±0.8) mV.The in vitro release behavior of the nanoparticles exhibited obvious redox-sensitivity.The results of in vitro cytotoxicity showed that the blank carrier material HACD had no obvious toxicity to hepatoma cells,and the HACD/DOX nanoparticles could effectively kill hepatoma cells with the 0.38 μg/ml half maximal inhibitory concentration (IC50) value at 48 h.Flow cytometry and CLSM results demonstrated that the HACD/DOX nanoparticles could target hepatoma cells through the mediating effect of hyaluronic acid.Conclusions The prepared HACD/DOX nanoparticles have suitable particle size,high drug loading and encapsulation efficiency,and can release DOX under the stimulation of reducing agent.These nanoparticles have obvious targeting effect on hepatoma cells,which is expected to be applied as the drug delivery system of hepatocellular carcinoma (HCC) therapy.

Objective To investigate whether the genetic variant rs10830963 of melatonin receptor 1B(MTNR1B)gene is associated with increased risk for gestational diabetes mellitus (GDM).Methods Eighty-seven GDM subjects(GDM group)and 91 normal pregnant women (control group)were randomly recruited form Women and Children's Hospital of Quzhou,Zhejiang Province,China.The allele and genotype frequencies of the rsi0830963 in MTNR1B gene were determined in all participants with PCR amplification and DNA sequencing.The allele and genotype frequencies of rs10830963 were compared to determine their differences between GDM subjects and normal controls.In addition,multiple linear regression was conducted to investigate the association patterns of the risk allele with fasting glucose and HbAlc levels.Results Both GG genotype and G allele frequencies of the rs10830963 loci in the GDM group were significantly higher than those in the controls,and women with G allele and GG genotype were associated with increased GDM risk(OR=1.53,95％ CI:1.005-2.324,P=0.047 and OR=2.16,95％ CI:1.052-4.434,P=0.034 respectively).After adjusting for age,body mass index before pregnancy,and family history of diabetes mellitus,women carrying GG genotype still had a higher GDM risk(OR =2.07,95％ CI:1.048-4.372,P =0.022).Multiple linear regression showed that the rs10830963 G allele was positively correlated with higher levels of fasting glucose(0.068 mmol/L,P=0.015)and HbAlc(0.073％,P=0.028).Conclusions Genetic variant rs10830963 in MTNR1B gene may contribute to the susceptibility to GDM in Chinese population and the rs10830963 G allele is a risk factor for the GDM susceptibility.