Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models / 中华劳动卫生职业病杂志

Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type Ⅲ collagen, transforming growth factor-β (TGF-β) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.

A C-type lectin containing two carbohydrate recognition domains participates in the antibacterial response by regulating the JNK pathway and promoting phagocytosis.

C-type lectins (CTLs) are important immune-related molecules in crustaceans. However, the immunologic mechanism by which CTLs eliminate invading pathogens is still unclear. In this study, we studied the antimicrobial mechanism of a CTL containing two carbohydrate recognition domains (DClec). After Aeromonas hydrophila challenge, several antimicrobial peptides (ALF1, ALF4, ALF5 and lys-i2) were upregulated. The transcript levels of ALF1, ALF4 and ALF5 were downregulated after A. hydrophila challenge in groups with DClec interference or inhibition compared with the control group. Similar results were obtained after c-Jun N-terminal kinase (JNK) interference. This finding indicates that DClec might regulate the JNK signalling pathway and subsequently adjust antimicrobial peptide (AMP) expression. Additionally, we found that DClec was secreted into the hemolymph. Recombinant protein DClec (rDClec) agglutinated gram-positive or gram-negative bacteria. Both rDClec and the native DClec in hemolymph bound to different bacteria. In this process, Ca2+ promoted the rDClec bacterial binding ability. After DClec interference, the phagocytosis ability of hemocytes was lower than that of the control group. Therefore, DClec can facilitate bacterial elimination by promoting AMPs expression and hemocyte phagocytosis.

Pharmacological activities of berberine and strategies to improve its oral bioavailability / 药学学报

Berberine is a naturally occurring benzylisoquinoline alkaloid with a wide range of pharmacological activities, such as antibacterial, anticancer, hypolipidemic, antidiabetic and antidiarrheal. Although berberine has a wide range of curative effects, the extremely low bioavailability (< 1%) limits its clinical application. Pure berberine preparations have not yet been approved for any specific disease. The low oral bioavailability of berberine is mainly due to poor solubility caused by self-aggregation under acidic conditions, low permeability, P-glycoprotein (P-gp)-mediated efflux, and liver and intestine metabolism. To improve the oral bioavailability of berberine, researchers have adopted a variety of strategies, including the application of various nano-delivery systems, penetration enhancers and P-gp inhibitors, structural modifications, and development of berberine derivatives. Improving the oral bioavailability of berberine can improve the pharmacological activity of berberine, reduce the dosage, and then reduce the toxic and side effects. This review summarized the various pharmacological activities, metabolism progress and pharmacokinetic characteristics of berberine, the newly discovered berberine target intestinal microbiota and focused on the strategies to improve the oral bioavailability of berberine by improving solubility and permeability, inhibiting P-gp efflux, and structural modification. The research on berberine was prospected, which provided guidance for the in-depth study of berberine.

Study of intermolecular interactions of piroxicam polymorphs / 药学学报

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats / 中华劳动卫生职业病杂志

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

A time-dependent density functional theory study of a fluorescent probe to detect hydroxyl radicals: Inhibiting the twisted intramolecular charge-transfer process.

Due to the relevance to excited-state processes, sensing mechanisms of fluorescent probes were difficult to study directly by experimental methods. This work investigated theoretically the sensing mechanism of a reported bifunctional fluorescent probe to detect intracellular hydroxyl radicals and their environmental viscosity (J. Am. Chem. Soc. 2019, 141, 18301). Calculations were performed at the B3P86/TZVP/SMD level using density functional theory and time-dependent density functional theory. The transition from the ground-state (S0) to the first singlet excited state (S1) was calculated to have the largest oscillation strength for the probe. The wavelength that corresponded to the S0-S1 vertical excitation energy (427 nm) agreed well with the maximum absorption band at 400 nm in the ultraviolet-visible spectra. Theoretical results showed that the probe had two distinct geometries in the S0 and S1 states, respectively. This difference was caused by the different distributions of frontier molecular orbitals that were involved in the S0-S1 transition and corresponds to a twisted intramolecular charge transfer. The S1-state potential energy curve of the probe molecule confirmed that the twisted intramolecular charge transfer could proceed spontaneously with a potential barrier of only 12.20 kJ/mol. This result provided an irradiative approach for the probe molecule to dissipate the S1-state energy, which explained its fluorescence quenching. In contrast, the hydroxyl oxidation reaction changed frontier molecular orbitals of the probe molecule, which made its S1 state a local S1 state with a strong fluorescence emission. Precisely due to the mechanism, the hydroxyl radicals could be detected by changes in the fluorescence signal of the probe molecule.

Theoretical study on the sensing mechanism of a coumarin-based fluorescent probe for biological thiols.

The sensing mechanism of a reported fluorescence probe for cysteine, homocysteine and glutathione (Yin et al., 2018) has been investigated by time-dependent density functional theory. Experimental absorption and emission spectra of the probe before and after thiol addition were reproduced well by theoretical calculations, which validated the rationality of the method. Optimized geometries showed that the probe molecule had distinctly different geometries in its ground and excited states. It corresponded to the photoisomerization process and explained the weak fluorescence of the probe molecule. Moreover, by the potential energy curve scan, photoisomerization was further confirmed to be a spontaneous process with a barrier that barely existed. Frontier orbital analysis indicated that this photoinduced isomerization of the probe molecule derived from the antibonding character for lowest unoccupied molecular orbital at its CC double bond. In contrast, probe-thiol complexes exhibited similar geometries in their ground and excited states, which was responsible for the strong fluorescence of the probe with thiols. Due to distinct excited-processes, the probe can be used to sense thiols by monitoring the fluorescent change.

Advances in nanocrystal technology and its application to improve the pharmacological efficacy for poorly-water soluble drugs / 药学学报

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.

Preparation, characterization and improved solubility of ticagrelor salts / 药学学报

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5 mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR-and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.

Association study of single nucleotide polymorphism of rs284489 in the 8q22 region with primary open angle glaucoma in a Sichuan Han Chinese population / 中华实验眼科杂志

Objective:To investigate the association between rs284489 in the 8q22 region and primary open angle glaucoma (POAG) in Sichuan, and the association between rs284489 and gender difference.Methods:A case control study was adopted.A total of 894 Han Nationality POAG patients in Sichuan People's Hospital from September 2015 to March 2017 were included, and 994 control patients who participated in physical examination in the same period were included.All subjects had no blood relationship and all were Han Chinese.Each sample of 4 ml-peripheral blood was collected for extracting DNA and rs284489 information was obtained from NCBI website.Primers 5.0 software was used to design primers.Genotyping was performed by using a tailored "Chinese-Chip" for association analysis of the rs284489 in the 8q22 region.Genotype allele frequencies and Hardy-Weinberg equilibrium (HWE) were assessed by using χ2 test.Logistic regression was applied to adjust for gender differences between the cases and controls.The PS; Power and Sample Size Calculation (version 3.1.2) software was used to calculate statistical power.This study followed the Declaration of Helsinki.This study followed the guidelines for the collection of human genetic disease specimens issued by the Ministry of Health of China.The study protocol was approved by the Ethics Committee of Sichuan Provincial People's Hospital (No.2016-58). Results:The allele distribution of rs284489 was within the HWE for both case and control groups (both at P>0.05). The difference of the minor allele-G distribution between the case group and the control group was not significant (allelic P*=0.94, OR [95% CI] **=1.01[0.83-1.23]); To further investigate the association between rs284489 and POAG, four genetic models, including model 1 (AG vs. AA), additive model 2 (GG vs.AA), dominant model (GG+ AG vs.AA), and recessive model (GG vs.AG+ AA) were applied.There was no significant difference in the four genetic models between the case and control groups (adjusted P# additive model 1 =0.26, P# additive model 2 =0.54, P# dominant model =0.50, P# recessive model =0.25); the gender difference in this study was not associated with the polymorphism of rs284489 (adjusted P#=1.00, crude OR [95% CI]=1.00[0.88-1.14], adjusted OR [95% CI]=1.00 [0.87-1.14]). Conclusions:rs284489 is not statistically associated with POAG in a Sichuan Han Chinese population.

Association of TLR4 polymorphisms with primary open angle glaucoma in Chinese population / 中华实验眼科杂志

Objective:To detect whether Toll-like receptor 4 ( TLR4) polymorphisms contributed to primary open angle glaucoma (POAG) in a Chinese population. Methods:A Chinese cohort, including 799 unrelated POAG patients and 799 unrelated controls, was enrolled in our case-control association study. The data was collected at Sichuan Provincial People's Hospital from May 2014 to March 2018. TLR4 functional single nucleotide polymorphisms (SNPs), including rs4986790 and rs4986791, were genotyped by SNaPshot method. Genotype and allele frequencies of the two SNPs were evaluated. This study was approved by the Institutional Review Boards of the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (No.2016-58), and complied with the guidelines of the Declaration of Helsinki. Written informed consents were obtained from all subjects prior to the study. Results:Allelic association analysis revealed that there were no significant association detected in the allelic distributions between the POAG cases and controls for SNPs rs4986790 ( P=0.317) and rs4986791 ( OR=1.000, 95% CI =0.062 5-16.002 2, P=1.000) in the TLR4 gene. Conditional analysis of the two SNPs did not show any significant difference in genotype and allele frequency between the case and the control groups. No association of the two SNPs with POAG was detected under four different genetic models, including homozygote, heterozygote, dominant and recessive models. Conclusions:Polymorphisms rs4986790 and rs4986791 in the TLR4 gene are not related to POAG in the Chinese cohort.

Influence of laparoscopic radical gastrectomy on clinical stress parameters and postoperative complications in patients with gastric cancer / 局解手术学杂志

Objective To investigate the effect of the laparotomy and laparoscopic surgery on the stress parameters and complication of patients with gastric cancer. Methods A total of 96 patients diagnosed as gastric cancer and treated by surgery in our hospital from January 2015 to January 2017 were divided into open operation group and laparoscopy group according to the operation method,48 cases in each group. Compared the operation time,bleeding volume,dissected lymph node number,postoperative hospitalization duration and anus exhausting time and complications in 6 months after surgery. The levels of WBC,CRP,TNF-α, IL-6 in serum before and after operation were detected by enzyme - linked immuno sorbent assay and compared. Results Compared with the open operation group, the bleeding volume,postoperative hospitalization duration and anus exhausting time of laparoscopy group were better with less dissected lymph node number and longer operation time, the differences were extremely significant(P ＜ 0. 01); the WBC,CRP,TNF-α, IL-6 levels of laparoscopy group at 1 day after the operation were lower than those of open operation group(P ＜ 0. 05). The incidence of complication of laparoscopy group was 22. 8％, which was less than 54. 7％ of control group, the difference was significant(P ＜ 0. 05). Conclusion Compared with the traditional open operation, laparoscopic radical gastrectomy can shorten the hospital stays and reduce the intraoperative blood loss, the stress response and complication rate after operation.

Association of ABCA1 rare nonsynonymous variants with primary open angle glaucoma / 中华实验眼科杂志

Objective To explore the rare nonsynonymous variants of ABCA1 gene in primary open angle glaucoma (POAG).Methods A prospective cohort study was carried out.Three hundred and ninety-eight POAG patients and 198 healthy controls matched in age and gender were recruited from March 2017 to March 2018 in Eye and Ear Nose Throat (ENT) Hospital of Fudan University.The periphery blood of 2-5 ml from all the subjects was collected for extraction of DNA,and rare variant analysis of the ABCA1 gene was conducted by whole exome sequencing (WES) data of these subjects.The study protocol was approved by Ethic Committee of Eye and Ear Nose Throat Hospital of Fudan University and Sichuan Provincial People's Hospital (No.2016-32-1,and written informed consent was obtained from each subject prior to entering the study cohort.Results A total of 21 rare nonsynonymous variants (minor allele frequency MAF＜0.O1) were detected in the coding regions of ABCA1 gene in 27 subjects of the 398 POAG,with the detection rate of 6.8％.Among them,c.4310C＞A (p.Thr1437Asn),c.3772G＞T(p.Asp1258Tyr),c.775A＞G (p.Lys259Glu) and c.1507_1508insGAGGT (p.Glu503GlyfsX7) were four novel variants.In the 198 healthy controls,five rare nonsynonymous variants were detected in the ABCA1 gene from five subjects respectively,with the detection rate of 2.5％,the detection rate of nonsynonymous in POAG group was higher than that in healthy control group,showing a significant difference (x2=4.72,P =0.03,OR =2.81).Conclusions Rare nonsynonymous variants in ABCA1 is associated with the pathogenesis of POAG.These variants can enrich the variation spectrum of ABCA1.

Analysis of FBN1 gene mutations in two pedigrees affected with Marfan syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS).@*WETHODS@#Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein.@*RESULTS@#Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein.@*CONCLUSION@#The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.

Analysis of MYOC gene variants among sporadic patients with primary open-angle glaucoma / 中华医学遗传学杂志

OBJECTIVE@#To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG).@*METHODS@#For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene.@*RESULTS@#Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis.@*CONCLUSION@#Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.

A Mussel-Inspired Facile Method to Prepare Multilayer-AgNP-Loaded Contact Lens for Early Treatment of Bacterial and Fungal Keratitis.

The use of contact lenses for the early treatment of bacterial or fungal keratitis has become a new research focus. Two main requirements of the therapeutic contact lenses are antimicrobial ability and visible light transmittance. Silver nanoparticles (AgNPs), as a nonspecific antimicrobial component, have been loaded onto contact lenses for the treatment of bacterial and fungal keratitis. Recently, it was reported that, via a simple immersion method, AgNPs can be synthesized and fixed onto the surface of polydopamine (PDA)-coated materials. However, in this study, we found that the above traditional method has the disadvantages of poor AgNP loading and low visible light transmittance, which could be induced by a limited amount of phenolic hydroxyl groups on and second oxidation of the PDA coating, respectively. To overcome these disadvantages, in this paper, we provided a facile and novel method to robustly bind multilayer-AgNPs on contact lens surfaces by using dopamine as a reducing agent and bioglue. In comparing with the monolayer-AgNP-loaded contact lenses fabricated by the traditional method, the multilayer-AgNP-loaded contact lenses had excellent antimicrobial ability and better visible light transmittance. Moreover, the multilayer-AgNP-loaded contact lens had low cytotoxicity to human corneal epithelial cells and anti-inflammation properties. Furthermore, the shortcoming of decreasing visible light transmittance induced by excess adherence of AgNPs on the multilayer-AgNP-loaded contact lens was alleviated by decreasing the size of AgNPs through altering the concentration of dopamine and AgNO3. Contact lenses loaded with small AgNPs (Ag@PDA-2.5, diameter ≈ 25-50 nm) had approximately the same Ag+ release and antimicrobial abilities, but significantly better visible light transmittance and anti-inflammatory properties than the contact lenses loaded with large AgNPs (Ag@PDA-5, diameter ≈ 50-75 nm). After that, in vivo testing indicated the promising therapeutic strategy of multilayer-AgNP-loaded contact lenses (Ag@PDA-2.5) for early bacterial keratitis and fungal keratitis. In addition, PDA coating could provide reactive sites to immobilize other biomolecules or drugs on this multilayer-AgNP-loaded contact lens for further combination therapies in treating bacterial or fungal keratitis. Finally, the stability of the visible light transmittance of the multilayer-AgNP-loaded contact lens was detected. The visible light transmittance of Ag@PDA-2.5 was weakened after being cultured with an extremely high concentration of bacteria, while it was stable in the moderate work environment. Though PDA coating had been wildly used to modify implantation devices, however, few studies about PDA coating modified contact lenses have been reported so far. Therefore, this research also provides an important basis for using PDA coating to modify a therapeutic contact lens.

Mutation analysis of FBN1 gene in a child with Marfan syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.</p><p><b>METHODS</b>The 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.</p><p><b>RESULTS</b>A novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.</p><p><b>CONCLUSION</b>The novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.</p>

Association of ZP4 gene polymorphism with primary open-angle glaucoma in an ethnic Chinese population from Sichuan province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province.</p><p><b>METHODS</b>A dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls.</p><p><b>RESULTS</b>No significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05).</p><p><b>CONCLUSION</b>ZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.</p>

Study of the expressions of NF-κB and MTA2 in infiltrating ductal carcinoma of breast and their correlation / 国际检验医学杂志

Objective To investigate the expression of NF-κB and MTA2 in infiltrating ductal carcinoma of breast and their correlations to clinicopathologic character.Methods The expressions of and MTA2 in breast cancer and paired adjacent normal breast tissues of 68 breast invasive ductal cancer patients were detected by real-time quantitative PCR method,and their correlations to the clinicopathologic characteristics of breast invasive ductal cancer were analyzed.Results The expressions of NF-κB and MTA2 in breast invasive ductal carcinoma were not related to age,tumor size and histological stage (P＞0.05),and were positively correlated with lymph node metastasis and TNM stage (P＜0.05).In addition,MTA2 was highly expressed in the tissues of ER positive breast invasive ductal cancer patients (P＜0.05).There was a positive correlation between the expression of NF-κB and the expression of MTA2 in breast cancer tissue of the infiltrating ductal carcinoma of breast patients(r=0.808,P=0.012).Conclusion Measurement of NF-κB and MTA2 from breast invasive ductal carcinoma tissue may provide a theoretical basis for the diagnosis,progression and prognosis of infiltrating ductal carcinoma of breast.