Synthesis of Isoxazol-5(2H)-one Derivatives via (tBuO)2Mg Promoted [3 + 2] Annulations of δ-Acetoxy Allenoates with Hydroxylamine.

Herein, an efficient (tBuO)2Mg promoted [3 + 2] annulation of δ-acetoxy allenoates with N-benzylhydroxylamine has been developed. This method provides a concise and facile protocol to synthesize vinylated isoxazol-5(2H)-one derivatives stereospecifically in a broad substrate scope with high efficiency (31 examples, up to 87% yield).

Identification of ZIC2 as a Potential Biomarker Linked with the Clinical Progression and Immune Infiltration of Oral Cancer: A Multicenter Study.

Aim: To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results: All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions: We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

NHC-catalyzed formal [3 + 3] annulations of δ-acetoxy allenoates for the synthesis of 4H-pyran derivatives.

Herein, an N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] annulation of δ-acetoxy allenoates with 1C,3O-bisnucleophiles for the construction of 4H-(fused)pyrans has been developed. This protocol provides a facile method to synthesize highly functionalized 4H-pyrans and has a broad substrate scope (30 examples, up to 77% yield).

Clinicopathological value of hematopoietic cell kinase overexpression in laryngeal squamous cell carcinoma tissues.

Laryngeal squamous cell carcinoma (LSCC) is the most lethal cancer in head and neck tumors. Although hematopoietic cell kinase (HCK) has been proven to be an oncogene in several solid tumors, its roles in LSCC remain obscure. This is the first study to evaluate the clinical value of HCK in LSCC, with the aim of exploring its expression status and potential molecular mechanisms underlying LSCC. LSCC tissue-derived gene chips and RNA-seq data were collected for a quantitive integration of HCK mRNA expression level. To confirm the protein expression level of HCK, a total of 82 LSCC tissue specimens and 56 non-tumor laryngeal epithelial controls were collected for in-house tissue microarrays and immunohistochemical staining. Kaplan-Meier curves were generated to determine the ability of HCK in predicting overall survival, progress-free survival, and disease-free survival of LSCC patients. LSCC overexpressed genes and HCK co-expressed genes were intersected to preliminarily explore the enriched signaling pathways of HCK. It was noticed that HCK mRNA was markedly overexpressed in 323 LSCC tissues compared with 196 non-LSCC controls (standardized mean difference = 0.81, p < 0.0001). Upregulated HCK mRNA displayed a moderate discriminatory ability between LSCC tissues and non-tumor laryngeal epithelial controls (area under the curve = 0.78, sensitivity = 0.76, specificity = 0.68). The higher expression level of HCK mRNA could predict worse overall survival and disease-free survival for LSCC patients (p = 0.041 and p = 0.013). Lastly, upregulated co-expression genes of HCK were significantly enriched in leukocyte cell-cell adhesion, secretory granule membrane, and extracellular matrix structural constituent. Immune-related pathways were the predominantly activated signals, such as cytokine-cytokine receptor interaction, Th17 cell differentiation, and Toll-like receptor signaling pathway. In conclusion, HCK was upregulated in LSCC tissues and could be utilized as a risk predictor. HCK may promote the development of LSCC by disturbing immune signaling pathways.

Identification through machine learning of potential immune- related gene biomarkers associated with immune cell infiltration in myocardial infarction.

BACKGROUND: To investigate the potential role of immune-related genes (IRGs) and immune cells in myocardial infarction (MI) and establish a nomogram model for diagnosing myocardial infarction. METHODS: Raw and processed gene expression profiling datasets were archived from the Gene Expression Omnibus (GEO) database. Differentially expressed immune-related genes (DIRGs), which were screened out by four machine learning algorithms-partial least squares (PLS), random forest model (RF), k-nearest neighbor (KNN), and support vector machine model (SVM) were used in the diagnosis of MI. RESULTS: The six key DIRGs (PTGER2, LGR6, IL17B, IL13RA1, CCL4, and ADM) were identified by the intersection of the minimal root mean square error (RMSE) of four machine learning algorithms, which were screened out to establish the nomogram model to predict the incidence of MI by using the rms package. The nomogram model exhibited the highest predictive accuracy and better potential clinical utility. The relative distribution of 22 types of immune cells was evaluated using cell type identification, which was done by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. The distribution of four types of immune cells, such as plasma cells, T cells follicular helper, Mast cells resting, and neutrophils, was significantly upregulated in MI, while five types of immune cell dispersion, T cells CD4 naive, macrophages M1, macrophages M2, dendritic cells resting, and mast cells activated in MI patients, were significantly downregulated in MI. CONCLUSION: This study demonstrated that IRGs were correlated with MI, suggesting that immune cells may be potential therapeutic targets of immunotherapy in MI.

Phase Deflectometry for Defect Detection of High Reflection Objects.

A method for detecting the surface defects of high reflection objects using phase deflection is proposed. The abrupt change in the surface gradient at the defect leads to the change in the fringe phase. Therefore, Gray code combined with a four-step phase-shift method was employed to obtain the surface gradients to characterize the defects. Then, through the double surface illumination model, the relationship between illumination intensity and phase was established. The causes of periodic error interference were analyzed, and the method of adjusting the fringe width to eliminate it was proposed. Finally, experimental results showed the effectiveness of the proposed method.

Comparison of 25-gauge+ and 27-gauge+ micro-invasive vitrectomy for vitreoretinal diseases / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To comparatively analyze the efficacy and safety between 25-gauge(25G+)and 27G+ micro-invasive vitrectomy for the treatment of vitreoretinal diseases.METHODS: The clinical data of 89 cases(89 eyes)of vitreoretinal disease who received vitrectomy at our hospital from March 2019 to April 2022 were retrospectively analyzed. They were divided into two groups according to surgery. A total of 45 cases(45 eyes)who received 25G+ micro-invasive vitrectomy were included in group A, and 44 cases(44 eyes)who received 27G+ micro-invasive vitrectomy were included in group B. Vitrectomy time, operation time, preoperative and postoperative best corrected visual acuity(BCVA), intraocular pressure, subjective comfort evaluation results and complications of the both groups were analyzed.RESULTS: There were no differences in vitrectomy time of the two groups(P&#x003E;0.05), while the operation time of group B was shorter than that of group A(35.50±14.27min vs. 41.73±14.25min, P=0.042). The postoperative BCVA of the two groups were better than that before operation(P&#x003C;0.05), while there was no significant difference between two groups(P&#x003E;0.05). The postoperative intraocular pressure of the two groups was lower than that before operation(P&#x003C;0.05), and it was slightly lower than group B at 1 and 7d after operation(P&#x003C;0.05). As for the subjective comfort evaluation results, the scores of group A was higher than that of group B at 1d after operation(6.13±1.20 vs. 3.45±1.17, P&#x003C;0.001); and there were no differences between two groups at 7d after operation(2.18±1.01 vs. 1.93±0.87, P=0.215). During the follow-up, 7(16%)eyes of incision leakage occurred in group A, of which 6(13%)eyes were transient hypotony, and 10(22%)eyes had conjunctival chemosis. In the group B, there was no incision leakage and transient hypotony, while conjunctival chemosis occurred in 2(4%)eyes at 1d after operation.CONCLUSION: Both 25G+ and 27G+ micro-invasive vitrectomy can improve visual acuity, stabilize intraocular pressure and be safe in patients with vitreoretinal disease. However, 27G+ micro-invasive vitrectomy has less leakage, stable intraocular pressure, shorter operation time and lower incidence of conjunctival chemosis.

Upregulation of CCNB2 and Its Perspective Mechanisms in Cerebral Ischemic Stroke and All Subtypes of Lung Cancer: A Comprehensive Study.

Cyclin B2 (CCNB2) belongs to type B cell cycle family protein, which is located on chromosome 15q22, and it binds to cyclin-dependent kinases (CDKs) to regulate their activities. In this study, 103 high-throughput datasets related to all subtypes of lung cancer (LC) and cerebral ischemic stroke (CIS) with the data of CCNB2 expression were collected. The analysis of standard mean deviation (SMD) and summary receiver operating characteristic (SROC) reflecting expression status demonstrated significant up-regulation of CCNB2 in LC and CIS (Lung adenocarcinoma: SMD = 1.40, 95%CI [0.98-1.83], SROC = 0.92, 95%CI [0.89-0.94]. Lung squamous cell carcinoma: SMD = 2.56, 95%CI [1.64-3.48]. SROC = 0.97, 95%CI [0.95-0.98]. Lung small cell carcinoma: SMD = 3.01, 95%CI [2.01-4.01]. SROC = 0.98, 95%CI [0.97-0.99]. CIS: SMD = 0.29, 95%CI [0.05-0.53], SROC = 0.68, 95%CI [0.63-0.71]). Simultaneously, protein-protein interaction (PPI) analysis indicated that CCNB2 is the hub molecule of crossed high-expressed genes in CIS and LC. Through Multiscale embedded gene co-expression network analysis (MEGENA), a gene module of CIS including 76 genes was obtained and function enrichment analysis of the CCNB2 module genes implied that CCNB2 may participate in the processes in the formation of CIS and tissue damage caused by CIS, such as "cell cycle," "protein kinase activity," and "glycosphingolipid biosynthesis." Afterward, via single-cell RNA-seq analysis, CCNB2 was found up-regulated on GABAergic neurons in brain organoids as well as T cells expressing proliferative molecules in LUAD. Concurrently, the expression of CCNB2 distributed similarly to TOP2A as a module marker of cell proliferation in cell cluster. These findings can help in the field of the pathogenesis of LC-related CIS and neuron repair after CIS damage.

[Application of personalized digital analog assisted acetabular prosthesis precise implantation in Crowe typeâ and â ¡ hip dysplasia].

OBJECTIVE: To explore the effect of personalized digital analog assisted acetabular prosthesis precise implantation in hip dysplasia. METHODS: From February 2017 to July 2019, 11 patients(12 hips) with hip dysplasia underwent total hip arthroplasty, including 4 males(5 hips) and 7 females(7 hips), aged from 27 to 61 years old, with an average of (46.64±12.93) years old;Crowe classification:8 hips in typeⅠ and 4 hips in typeⅡ. The preoperative thin-layer CT scan was imported into Mimics 10.01 software. The appropriate size and placement angle of acetabular prosthesis were selected through preoperative simulation, and the acetabular bone defect was understood to determine whether structural bone grafting was needed during the operation. The length of both lower limbs, the anteversion angle of acetabular prosthesis, the abduction angle, the height of acetabular rotation center and the horizontal distance of hip joint center before and after the operation were measured, and the postoperative dislocation, bone graft healing and acetabular cup loosening were observed. The hip Harris score was used to evaluate the joint function. RESULTS: All patients were followed up for 18 to 30 months with an average of (23.45±3.70) months. There was no prosthesis dislocation, loosening and bone graft healing after operation. One case had numbness in the innervation area due to the traction of sciatic nerve during operation, and was treated with neurotrophic drugs and recovered one month after operation. The length difference of both lower limbs decreased from (31.73±5.98) mm before operation to (4.73±1.90) mm 3 months after operation (t=15.268, P<0.01). The anteversion angle of acetabular cup and acetabulum was (17.45±3.62)°and abduction angle was (40.10 ± 2.30)° after operation. In all cases, the abduction angle and anteversion angle were within the safe range of Lewinek. The height of hip rotation center was (20.64±2.58) mm and the horizontal inward displacement of hip was (33.46±3.61) mm. Harris score increased from (45.36±2.34) before operation to (91.27±2.37) 3 months after operation (P<0.05). CONCLUSION: Through preoperative personalized digital analog reconstruction of acetabulum in patients with hip dysplasia, we can better understand the acetabular defect, help to evaluate the size and placement angle of acetabular prosthesis and whether structural bone grafting is needed, and obtain satisfactory clinical curative effect.

Clinical assessment and molecular mechanism of the upregulation of Toll-like receptor 2 (TLR2) in myocardial infarction.

OBJECTIVE: The prevalence and mortality of cardiovascular diseases remain ranked first worldwide. Myocardial infarction (MI) is the central cause of death from cardiovascular diseases, seriously endangering human health. The clinical implication of toll-like receptor 2 (TLR2) remains contradictory, and its mechanism is still unknown. Hence, the objective of this study was to elucidate the clinical value and molecular mechanism of TLR2 in MI. METHODS: All high-throughput datasets and eligible literature were screened, and the expression levels of TLR2 were collected from the MI. The integrated expression level of TLR2 was displayed by calculating the standardized mean difference (SMD) and the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC). The related TLR2 genes were sent for pathway analyses by gene ontology (GO), Kyoto encyclopedia of genes and genome (KEGG), and disease ontology (DO). Single-cell RNA-seq was applied to ascertain the molecular mechanism of TLR2 in MI. RESULTS: Nine microarrays and four reported data were available to calculate the comprehensive expression level of TLR2 in MI, including 325 cases of MI and 306 cases of controls. The SMD was 2.55 (95% CI = 1.35-3.75), and the AUC was 0.76 (95% CI = 0.72-0.79), indicating the upregulation of TLR2 in MI. The related TLR2 genes were primarily enriched in the pathways of atherosclerosis, arteriosclerotic cardiovascular disease, and arteriosclerosis, suggesting the clinical role of TLR2 in the progression of MI. Afterward, TLR2 was upregulated in myeloid cells in MI. CONCLUSIONS: TLR2 may have a crucial role in progressing from coronary atherosclerosis to MI. The upregulation of TLR2 may have a favorable screening value for MI.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip.

BACKGROUND: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. RESULTS: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. CONCLUSIONS: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.

Linggui Zhugan Formula Improves Glucose and Lipid Levels and Alters Gut Microbiota in High-Fat Diet-Induced Diabetic Mice.

Background: The gut microbiota plays important roles in the occurrence and development of obesity and diabetes through participating in nutrient absorption and metabolism. Microecological regulation is likely to be key to understanding the effects of Chinese medicine. The Linggui Zhugan (LGZG) formula is a well-known Chinese medicine for controlling obesity in the clinic. However, its pharmacological effects and mechanism of action in diabetes require further exploration. Objective: To evaluate the effects of LGZG on body weight, glycemic control, lipid levels, and gut microbiota in high-fat diet-induced diabetic mice. Methods: High-fat diet-induced diabetic mice were subjected to an 8-week protocol of LGZG administration. We then evaluated the pharmacological effects of LGZG and its influence on gut microbes in fecal samples using the 16S rRNA-based microbiome profiling technique. Results: LGZG administration significantly reduced body weight and body fat mass in diabetic mice. Compared with the high-fat diet control group, LGZG favorably influenced blood glucose control, decreased blood glucose levels, and increased glucose tolerance, accompanied by an improvement in lipid metabolism. Furthermore, the global community composition and relative abundance of many taxa differed between mice fed chow or a high-fat diet. As expected, LGZG supplementation altered the general community structure of gut microbiota, the Firmicutes/Bacteroidetes ratio, and the relative abundance of certain bacteria, such as Bacteroides, Lactobacillus, Oscillospira, and Helicobacter. Conclusion: LGZG effectively controlled obesity and relieved insulin resistance, which may be closely related to its impact on gut microbiota.

Upregulation of JHDM1D-AS1 protects PDLSCs from H2O2-induced apoptosis by decreasing DNAJC10 via phosphorylation of eIF2α.

Periodontal ligament stem cells (PDLSCs) are a promising tool for regenerative medicine in clinical periodontal ligament repair. However, clinical maintenance of high quality and large quantity of PDLSCs faces multiple obstacles. One of them is how PDLSCs respond to environmental stimuli such as reactive oxygen species. We aim to elucidate how PDLSCs react to oxidative stress and the underlying mechanisms. We utilized hydrogen peroxide-induced oxidative stress to mimic ROS increase in rat PDLSCs. Our data indicated a rapid downregulation of a long non-coding RNA, lncRNA JHDM1D antisense 1 (JHDM1D-AS1), when PDLSCs were treated with hydrogen peroxide, which was negatively associated with PDLSC apoptosis. Moreover, our data showed that JHDM1D-AS1 regulated PDLSC apoptosis via inhibition of DNAJC10, a heat shock protein 40 family member. Moreover, overexpressed DNAJC10 inhibited Bcl-2 protein level and eIF2α phosphorylation level, which, in turn, contributed to PDLSC apoptosis. Our results revealed a protective role of JHDM1D-AS1 in ROS-induced apoptosis, and validated that JHDM1D-AS1/DNAJC10/phosphorylated-eIF2α/Bcl-2 pathway works as an anti-apoptotic signaling axis in PDLSCs.These findings will facilitate the in vitro culturing of PDLSCs for clinical usage and promote stem cell-based therapy for periodontal tissue regeneration.

Effects of Health Qigong Baduanjin on diabetes related indexes in middle-aged obese women / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of Health Qigong Baduanjin on the related indexes of obese middle aged women with diabetes and to provide new ideas for the intervention treatment of diabetes.@*METHODS@#A total of 40 middle-aged female obese diabetic patients were randomly divided into the control group and the exercise group(=20), the age was(57.2±5.4) years old. Fitness training group performed eight new Baduanjin exercises for 24 weeks of intervention, the control group did not exercise, body weight, waist circumference, body mass index (BMI), waist hip ratio (WHR), fasting blood glucose (FPG), glycosylated hemoglobin (HbAlc), triglyceride(TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) levels and serum retinol binding protein 4(RBP4) index were observed in the two groups.@*RESULTS@#After exercise, the waist, WHR, FPG, TG, HbAlc, HDL and RBP4 levels of the the patients in the experimental group were decreased significantly compared with those of before exercise and those of the patients in the experimental control group before and after exercise (<0.05).@*CONCLUSIONS@#Health Qigong Baduanjin can reduce the blood sugar of obese female patients with diabetes, and has some improvement effect on the body part of obesity and blood lipid indicators.

TIPE2 expression is increased in peripheral blood mononuclear cells from patients with rheumatoid arthritis.

We investigated the changes in mRNA and protein expression of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) and PEST-containing nuclear protein (PCNP) in peripheral blood lymphocytes from 54 patients with rheumatoid arthritis (RA) and the spleens of model mice with collagen-induced arthritis (CIA) to generate new ideas for clinical diagnosis and treatment. Expression levels of both TIPE2 and PCNP were higher in RA patients and CIA mice than in their respective controls. They were also higher in the 32 patients with active RA than in the 22 with inactive RA (P < 0.001 for both). After comprehensively treating patients with active RA with anti-inflammatory and antirheumatic drugs for 6 months, they were stable, and there was no difference in TIPE2 levels between the treated patients and those with inactive RA (P = 0.85). In addition, TIPE2 mRNA levels in peripheral blood correlated positively with PCNP (R2 = 0.744, P = 0.001). The DAS28 score correlated positively with peripheral blood TIPE2 levels in the RA patients (R2 = 0.945, P = 0.001). These findings suggest TIPE2 expression increases with the severity of RA.

The relationship between MMP-1 genetic polymorphisms and dental implant early failure in Chinese Han nationality / 重庆医学

Objective To make clear the relationship between the genetic polymorphism of MMP-1 and implant early failure.Methods We conducted a case control study,53 cases patients (no smoking history and without periodontitis) who have underwent dental implant were divided into experimental group(with dental implant failure) and control group(with dental implant success) according to early failure of dental implant (within one month).DNA of 53 patients in Han nationality were extracted by using Chelex-100 method and polymorphisms of the mmp-1-1607 gene were detected by restriction fragment length polymorphism after polymerase chain reactions.Results Patients with MMP-1-1607(1G/2G) genotype exhibited a significantly higher occurrence of implant early failure than those with MMP-1-1607(1G/1G) gene type(P＜0.05).The OR of the 1G/2G versus the 1G/1G of the MMP-1-1607 genotype was 13.894(P＜0.05).Conclusion MMP-1-1607(1G/2G) genotype is associated with implant early failure.

Efficacy of intravitreal ranibizumab or Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the efficacy of intravitreal ranibizumab or conbercept combined with macular laser grid photocoagulation(MLG)for macular edema secondary to branch retinal vein occlusion(BRVO).<p>METHODS: Totally 120 patients(120 eyes)with BRVO were randomized into three groups, 40 patients(40 eyes)in each group. Group A received MLG alone; Group B: intravitreal injection of ranibizumab 0.05mL/0.5mg; Group C: intravitreal injection of conbercept 0.05mL/0.5mg. MLG were performed in Group B and Group A at 1wk after injection. At 1mo after injection, all the patients were examined with fundus fluorescein angiography and optical coherence tomography, repeated injections were given if necessary. Repeated injection rate of Group B and C was compared after a six-month follow-up. before and at 1wk, 1, 3, 6mo after treatment, best corrected visual acuity(BCVA)and central macular thickness(CMT)of the two groups were analyzed.<p>RESULTS: In Group B, there were 4 eyes with 2 consecutive injections, 7 eyes with 3 consecutive injections, and the repeated injection rate was 27.5%. Patients in Group C received injection only once. The repeated injection rate of Group B was higher than that of Group C with significant difference(<i>P</i><0.05). BCVA of the three groups were improved after treatment, CMT was less than those before treatment. BCVA of Group B and C after treatment was better than those of Group A and CMT was less. BCVA of Group C was better than that of Group B, and CMT was less without significant difference(<i>P</i>>0.05). After the follow-up, there were no significant adverse reactions in three groups. The recurrence rate of group A was 25%, no recurrence in Group B and C and the difference was statistically significant(<i>P</i><0.05).<p>CONCLUSION: Intravitreal ranibizumab or Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion is effective. But injection times of Conbercept is less.

Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma.

Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2'-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

[Biomineralization of electrospun polycaprolactone-guided bone regeneration membrane].

OBJECTIVE: To evaluate the biomineralization of the tissue-engineering electrospun polycaprolactone (PCL) scaffold and its potential use for guided bone regeneration (GBR) membranes. METHODS: PCL ultrafinefiber scaffolds were fabricated by electrospinning and then immersed in supersaturated calcification solution (SCS) for biomineralization investigation. The electrospun PCL scaffolds and the calcium phosphate coating were identified by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Water-contact angles were also measured to evaluate the hydrophilicity of the modified surface. The biocompatibility of the composite was investigated by culturing osteoblasts on the scaffolds. Cell behavior was observed by SEM. RESULTS: The electrospun PCL scaffold was composed of ultrafine fibers and well-interconnected pores. The deposits on the fibers grew in number and size as the biomineralization time increased. Then, the covering of the whole PCL film was identified as dicalcium phosphate dehydrate and apatite. Good cell attachment and proliferation behavior were observed on the membranes. CONCLUSIONS: The quick apatite formation on the surface of the PCL electrospun scaffold indicated that SCS biomineralization may be an effective approach for obtaining PCL/calcium phosphate composites. The cellular biocompatibility of the composite scaffold was preliminarily confirmed by the in vitro culture of osteoblasts on the scaffold. As such, the composite scaffold is a promising biomimetic extracellular matrix biomaterial for bone tissue engineering and GBR membranes.