Choroidal neovascularization(CNV)is one of common causes of vision loss.The pathogenesis and development of CNV are a comprehensive process which is regulated by multiple factors and cytokines.Cyclooxygenase-2(COX-2)is an inducible isoform of cyclooxygenase and rate limiting enzyme in the prostaglandin biosynthesis pathway.COX-2 plays an important role in neovascularization by modulating vascular endothelial growth factor(VEGF),migration and apoptosis of endothelial cell.Recently,some experimental studies demonstrated that COX-2 involves in the information of CNV and the inhibitor of COX-2 can suppress CNV.These results provide a new prospect for the prevention and treatment of the CNV.Biological characteristics of COX-2 and its relationship with CNV are reviewed in this article.

Objective Our previous study showed that cycloxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are expressed in choroidal neovascularization (CNV) and the expression of COX-2 is prior to VEGF, indicating that COX-2 is probably one of upstream regulatory factors of VEGF. The aim of this study was to observe inhibition and mechanism of intravitreous injection of celecoxib, a selective COX-2 inhibitor, on experimental choroidal neovascularization in a laser-induced rat model. Methods Retinal photocoagulation was performed in 36 right eyes of 36 male Brown Norway rats to establish CNV models with the laser parameter as follows:wavelength 532 nm, power 80 mW, spot diameter 100 p, m and time shutter 100 ms. Eight or ten spots were irradiated in the position of 1.5 - 2. 0 PD to optic disc. Celecoxib or normal saline solution was intravitreously injected via scleral incision in 18 right eyes of 18 rats, respectively. The thickness and area of CNV were qualified by HE staining(n =3) and by choroidal flatmount (n =3) at day 14 after photocoagulation under the light microscope. The expressions of VEGF and COX-2 in RPE-choroid-sclera complex were examined by Western blot(n =6) and RT-PCR(n =6) at day 7 after photocoagulation. The experimental procedure followed the Standard of Association for Research in Vision and Ophthalmology. The license for animal administration was obtained. Results After intravitreous injection with celecoxib, the thickness and area of CNV were significantly smaller in celecoxib group than normal saline group on 14 days (69. 75 μm ± 7. 50 μm vs 45. 84 μm ± 5. 59 μm in thickness and 87 854 pixel~2 ± 6 735 pixel~2 vs 61 101 pixel~2 ± 6 314 pixel~2 in area, P =0.00). The expressions of VEGF protein and mRNA were obviously lower in celecoxib group compared with normal saline group(t = 3. 755, P = 0.02; t =3. 155, P =0. 03) . No significant difference was found in expression of COX-2 mRNA between the two groups (t = 0. 581, P = 0. 59). Conclusion Intravitreous injection of celecoxib can effectively inhibit CNV by downregulating VEGF level, which is a new approach for the treatment of CNV.

Objective To compare the differences of hospital stays,hospitalization costs and effectiveness via keyhole hematoma debridement (KHED) and internal medicine conservative treatment (IMCT) in treating 30-40 mL hypertensive intracerebral hemorrhage.Methods Fifty-eight patients with hypertensive intracerebral hemorrhage whose bleeding was 30-40 mL,admitted to our hospital from January 2014 to September 2015,were chosen in our study;according to the will of the patients and their family members,the patients were divided into KHED group (n=31) and IMCT group (n=27).The differences of hospital stays,hospitalization costs,neurological dysfunction rate at hospital and three months after discharge,and recovery results were compared between the two groups.Results The average hospital stays of KHED group were (7.4±2.3) d and those of IMCT group were (14.5±5.1) d,with significant difference (P=0.012);the hospitalization costs for the two groups were (36 296.28±5292.12)yuan,and (41 769.48±6342.83) yuan,with significant difference (P=0.027).Glasgow outcome scale of KHED group at discharge indicated 29 patients with good recovery and 2 with poor recovery;that of IMCT group indicated 20 with good recovery and 7 with poor recovery,including two with cerebral edema accepted craniotomy operation in second time.Follow-up for three months showed that the KHED group had basic activities of daily living in 16 patients,mild hemiplegia in 11 and severe hemiplegia in 4,and IMCT group had basic activities of daily living in 9 patietns,mild hemiplegia in 13 and severe hemiplegia in 5;significant differences were noted between the two groups (Z=2.499,P=0.001).Conclusion KHED in treatment of 30-40 mL hypertensive intracerebral hemorrhage can shorten hospitalization time,reduce cost,have better prognosis and better short-term and long-term effectiveness than IMCT.

Objective: To compare the surgical accuracy of the 3D printing surgical guide and traditional occlusal splint in the treatment of skeletal facial asymmetry cases. Methods: 12 facial asymmetric patients underwent joint orthognathic and orthodontics treatments were included in this research. In the 3D printing group (n=6) the pre-surgical CT scan for the skeleton and laser scan for the dentures were performed and 3D orthognathic procedures including Le FortⅠ and BSSRO combined with genioplasty were planned. The 3D printing surgical guides were manufactured and applied during surgeries. Another 6 cases were received same procedures by traditional occlusal splint techniques as the control group. Post-surgical CT reconstruction and 3D superimposition with pre-surgical planning was carried out for outcome comparison. Results: The maximal error of maxillar was 0.65 mm and average error was less than 1 mm in 3D printing group, while the maxillary maximal error was 2.11 mm and average error was greater than 1 mm in traditional group which showed the statistical significance (P<0.05). Conclusions The usage of 3D printing surgical guide could improve the orthognathic surgical precision by controlling the jaw bone in a three-dimensional way.

OBJECTIVETo establish a long-standing cell line of esophageal squamous cell carcinoma (ESCC) in pursuit of a model for in vitro study of carcinogenesis.

METHODSSmall tissue blocks taken from resected specimens of esophageal cancer were cultured, and cell line EC9706 was established. The biologic properties of EC9706 were characterized. Comparative genomic hybridization(CGH) was performed on the cell line.

RESULTSThe growth curve of EC9706 was detected. The cell generation time was 26 hours. The plate colony forming efficiency is 91.9%, with the capacity of forming clones in soft agar. EC9706 cells show high tumorigenecity as indicated by the rapid regeneration of moderate-poor-differentiated squamous cell carcinomas after injection into nude mice. CGH analysis indicated copy number gains of 1p1, 1q2-4, 2p1, 2q1, 5p, 7p14, 7q21, 11q1, 15q2, 20q and losses of 2p2, 2q2, 3p, 4, 9p, 14, 18, Xq. High-level gain of 5p was observed.

CONCLUSIONEstablished cell line EC9706 can serve as a useful tool for studying the carcinogenesis of ESCC.

Aged ; Animals ; Carcinoma, Squamous Cell ; genetics ; pathology ; Cell Division ; Chromosome Aberrations ; Esophageal Neoplasms ; genetics ; pathology ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Nucleic Acid Hybridization ; methods ; Transplantation, Heterologous ; Tumor Cells, Cultured

BACKGROUNDThe bacterial endotoxins test (BET) is a method used to detect or quantify endotoxins (lipo-polysaccharide, LPS) and is widely used in the quality control of parenteral medicines/vaccines and clinical dialysis fluid. It is also used in the diagnosis of endotoxemia and in detection of environment air quality control. Although BET has been adopted by most pharmacopoeias, result judgment algorithms (RJAs) of the test for interfering factors in the BET still differ between certain pharmacopoeias. We have evaluated RJAs of the test for interfering factors for the revision of BET described in the Chinese Pharmacopoeia 2010 (CHP2010).

METHODSOriginal data from 1 748 samples were judged by RJAs of the Chinese Pharmacopoeia 2010, the Japanese Pharmacopoeia 2011 (JP2011), the European Pharmacopoeia 7.0 (EP7.0), the United States Pharmacopoeia 36 (USP36), and the Indian Pharmacopoeia 2010 (IP2010), respectively. A SAS software package was used in the statistical analysis.

RESULTSThe results using CHP2010 and USP36, JP2011, EP7.0, and IP2010 had no significant difference (P = 0.7740). The results using CHP2010 of 1 748 samples showed that 132 samples (7.6%) required an additional step; nevertheless there was no such requirement when using the other pharmacopeias. The kappa value of two RJAs (CHP2010 and EP7.0) was 0.6900 (0.6297-0.7504) indicating that the CHP2010 and other pharmacopoeias have good consistency.

CONCLUSIONSThe results using CHP2010 and USP36, JP2011, EP7.0, and IP2010 have different characteristics. CHP2010 method shows a good performance in Specificity, mistake diagnostic rate, agreement rate, predictive value for suspicious rate, and predictive value for passed rate. The CHP2010 method only had disadvantages in sensitivity compared with other pharmacopeias. We suggest that the Chinese pharmacopoeia interference test be revised in accordance with the USP36, JP2011, EP7.0, and IP2010 judgment model.

Adult ; Algorithms ; Asian Continental Ancestry Group ; Diskectomy ; Endotoxins ; metabolism ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Intervertebral Disc Displacement ; surgery ; Low Back Pain ; surgery ; Male ; Middle Aged ; Retrospective Studies

Endotoxemia ; diagnosis ; Endotoxins ; analysis ; Humans ; Sepsis ; diagnosis

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology* ; Cellular Senescence ; Homeostasis ; Cell Cycle Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; Mitochondria/metabolism* ; Electron Transport Complex III/metabolism* ; Humans ; Cells, Cultured

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.