The association between vitamin D and the progression of diabetic nephropathy: insights into potential mechanisms.

Aims: Vitamin D deficiency (VDD) is prevalent in the population, with inadequate intake, impaired absorption and metabolism as the main causative factors. VDD increases the risk of developing chronic diseases such as type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), but the molecular mechanisms underlying this phenomenon are not known. The aim of this study was to investigate the association and potential mechanisms of vitamin D levels with the progression of DN by analyzing general clinical data and using bioinformatics methods. Methods: The study included 567 diabetes mellitus type 2 (T2DM) patients from the Rocket Force Characteristic Medical Center as the case group and 221 healthy examinees as the normal control group. T2DM patients were categorized into T2DM, early diabetic nephropathy (EDN), and advanced diabetic nephropathy (ADN) based on the progression of diabetic nephropathy. The renal RNA-seq and scRNA-seq data of patients with DN were mined from public databases, and the differential expression of vitamin D-related genes in normal-EDN-ADN was analyzed by bioinformatics method, protein interaction network was constructed, immune infiltration was evaluated, single cell map was drawn, and potential mechanisms of VD and DN interaction were explored. Results: Chi-square test showed that vitamin D level was significantly negatively correlated with DN progression (p < 0.001). Bioinformatics showed that the expression of vitamin D-related cytochrome P450 family genes was down-regulated, and TLR4 and other related inflammatory genes were abnormally up-regulated with the progression of DN. Vitamin D metabolism disturbance up-regulate "Nf-Kappa B signaling pathway," B cell receptor signaling pathway and other immune regulation and insulin resistance related pathways, and inhibit a variety of metabolic pathways. In addition, vitamin D metabolism disturbance are strongly associated with the development of diabetic cardiomyopathy and several neurological disease complications. Conclusion: VDD or vitamin D metabolism disturbance is positively associated with the severity of renal injury. The mechanisms may involve abnormal regulation of the immune system by vitamin D metabolism disturbance, metabolic suppression, upregulation of insulin resistance and inflammatory signalling pathways.

Dihydroartemisinin suppresses the tumorigenesis of esophageal carcinoma by elevating DAB2IP expression in a NFIC-dependent manner.

Dihydroartemisinin (DHA) has been identified to have the anticancer and anti-inflammatory activities. Disabled homolog 2 interacting protein (DAB2IP) is a well-recognized tumor suppressor. Both DHA and DAB2IP were proven to have suppressing effects on esophageal carcinoma (ESCA) tumorigenesis. However, whether DHA regulated ESCA cells via DAB2IP and its mechanism are still vague. Functional analyses were conducted using MTT, tube formation, sphere formation, and transwell assays in vitro as well as Tumor formation experiments in mice. Levels of genes and proteins were assayed by qRT-PCR and western blotting analyses. The interaction between DAB2IP and Nuclear Factor I C (NFIC) was confirmed using bioinformatics analysis and dual-luciferase reporter assay. DHA treatment suppressed ESCA cell angiogenesis, stemmess, migration, and invasion. DAB2IP level was decreased in ESCA tissues and cells, and DHA elevated DAB2IP expression in ESCA cells. Functionally, DAB2IP overexpression impaired ESCA cell angiogenesis, stemmess, migration and invasion. Mechanistically, NFIC had binding sites on the promoter region and directly targeted DAB2IP. DHA could up-regulate DAB2IP expression via NFIC. Moreover, NFIC was also decreased in ESCA tissues and cells, and its overexpression had anticancer activity in ESCA cells. In addition, DAB2IP knockdown reversed the anticancer effects of NFIC or DHA on ESCA cells. In further in vivo analysis, DHA also suppressed ESCA growth by regulating DAB2IP expression. DHA suppressed the tumorigenesis of ESCA by elevating DAB2IP expression in an NFIC-dependent manner, suggesting the potential clinical application of DHA in ESCA treatment.

LncRNA OIP5-AS1 Targets the miR-140-5p/UBR5 Cascade to Promote the Development of Gastric Cancer.

Gastric cancer (GC) is a malignant tumor with the highest incidence among all kinds of malignant tumors in China. Long noncoding RNAs (LncRNAs) have been reported to act as microRNA (miRNAs) sponges and thus play key roles in biological processes and pathogenesis. Thus, this study aimed to investigate the functional effects and the regulatory mechanism of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in gastric cancer cells. The expression of OIP5-AS1, miR-140-5p, Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were assessed using Cell-Counting Kit-8 (CCK-8), Flow cytometry, and Transwell assays. UBR5 protein level was detected by Western blot. Binding between miR-140-5p and OIP5-AS1 or UBR5 was predicted by Starbasev2.0 and TargetScan, and verified using Dual-luciferase reporter assays and RNA pull-down assay. A xenograft mice model was used to evaluate the effects of OIP5-AS1 on tumor growth in vivo. OIP5-AS1 was upregulated in GC cancer and cells. OIP5-AS1 knockdown inhibited cell proliferation, migration, invasion, but induced cell apoptosis in GC. In mechanism, OIP5-AS1 might serve as a sponge for miR-140-5p to enhance UBR5 expression. Moreover, overexpression of miR-140-5p or UBR5 partly reversed the effects of OIP5-AS1 depletion on the progression of GC cells. Furthermore, OIP5-AS1 depletion also suppressed tumor growth in vivo. OIP5-AS1 silencing might suppress proliferation, migration, invasion, and induced apoptosis in GC cells by regulating the miR-140-5p/UBR5 axis.

[Comparative Analysis of Thromboelastogram and Coagulation Items in Mongolian Patients with Thrombosis].

OBJECTIVE: To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation. METHODS: The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed. RESULTS: The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT（r=0.186，r=0.152）. K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364，r=0.616，r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318，r=0.519，r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P<0.001), 0.336 (P<0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P<0.001), 0.289 (P<0.001) and 0.290 (P<0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P<0.001), 0.285 (P<0.001) and 0.302 (P<0.001), respectively. CONCLUSION: The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.

Abundant expression of ferroptosis-related SAT1 is related to unfavorable outcome and immune cell infiltration in low-grade glioma.

BACKGROUND: Low-grade glioma (LGG) is susceptible to ferroptosis, which is involved in TMZ resistance. Ferroptosis induction can enhance the sensitivity to TMZ and synergistically kill glioma cells. T cell-promoted tumor ferroptosis is a vital anti-tumor mechanism of immune checkpoint inhibitors. The SAT1 activation is closely related to ferroptosis upon ROS induction due to the upregulation of arachidonate 15-lipoxygenase (ALOX15) expression. METHODS: The expression of SAT1 in pan-cancer and corresponding normal tissue from the TCGA data portal was primarily explored. The landscape of SAT1 and immune cell infiltration and their corresponding gene marker sets in different tissues were further explored. Additionally, we evaluated the relationships between SAT1 and the clinicopathologic parameters of LGG, and the disease-specific survival (DSS), progression-free interval (PFI), and overall survival (OS) were also assessed using KM survival curves and multivariate analysis in LGG. Meanwhile, the Gene Set Enrichment Analysis (GSEA) was also implemented to determine the potential effect of the SAT1 gene in LGG. Furthermore, the predictive power of SAT1 was validated using an independent LGG cohort from the Chinese Glioma Genome Atlas (CGGA) data. RESULTS: In general, the expression of SAT1 is different between most tumors and their adjacent normal tissues. The results demonstrated that SAT1 expression is positively associated with TMB in LGG, BRCA, and THYM. The results displayed that the expression level of SAT1 is obviously correlated with the level of infiltrating macrophages and CD8 + T cells, and the levels of most immune gene sets were associated with the SAT1 expression in LGG. Interestingly, univariate and multivariate models significantly indicated that the OS and PFI of patients with LGG with high SAT1 levels were poorer than those with low SAT1 expression in the TCGA LGG cohort. GSEA showed that SAT1 was involved in immune regulation and multiple signaling pathways. Finally, our analysis demonstrated that SAT1 was closely associated with IDH mutation, 1p19q codeletion, chemoradiotherapy resistance and disease recurrence. CONCLUSIONS: Abundant expression of SAT1 was related to poor disease prognosis and abundant immune cell infiltration in LGG.

Exposure to Low-Dose Radiation Enhanced the Antitumor Effect of a Dendritic Cell Vaccine.

The unsatisfactory clinical efficacy of dendritic cell (DC)-based cancer vaccines prepared by conventional methods is partly due to their insufficient capacity for migration. Our previous study showed that exposure to low-dose radiation (LDR) at a dose of 0.2 Gy promoted DC migration in vitro. The present study further investigates whether exposure to LDR at a dose of 0.2 Gy during the DC vaccine preparation could increase the antitumor effect of DC vaccines derived from mouse bone marrow. Our results showed that the migratory capacities of DCs were significantly increased after exposure to LDR. Furthermore, exposure to LDR resulted in an increased ability of DCs to induce T-cell proliferation, and the cytotoxic effect of cytotoxic T lymphocytes (CTLs) primed by the DCs exposed to LDR was significantly enhanced. An in vivo study using a mouse transplanted tumor model showed that subcutaneous injections of a DC vaccine exposed to LDR led to an increased mouse survival rate, infiltration of CTLs into tumor tissue, and apoptosis of tumor cells, which were accompanied by significant upregulation of serum interferon γ and interleukin 12. These results indicate that exposing DCs to LDR during the DC vaccine preparation is an effective approach to enhance its antitumor effect.

Dendritic cell-based cancer immunotherapy for pancreatic cancer.

Pancreatic cancer (PC) is a lethal disease and remains one of the most resistant cancers to traditional therapies. New therapeutic modalities are urgently needed, particularly immunotherapy, which has shown promise in numerous animal model studies. Dendritic cell (DC)-based immunotherapy has been used in clinical trials for various cancers, including PC, because DCs are the most potent antigen-presenting cell (APC), which are capable of priming naive T cells and stimulating memory T cells to generate antigen-specific responses. In this paper, we review the preclinical and clinical efforts towards the application of DCs for PC.

Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.

For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

CARTs for Solid Tumors: Feasible or Infeasible?

Adoptive transfer of chimeric antigen receptor-engineered T cells (CARTs) is a novel approach to cancer therapy as CARTs combine with the antigen specificity of an antibody and the activating functions of T lymphocytes. Recent results from preclinical and clinical trials with CARTs for B-cell malignancies are exciting, although different groups selected different tumor-associated antigens, binding domains, and signal domains, which make up the chimeric antigen receptor (CAR) configuration. However, there are few clinical trials with CARTs for solid tumors compared to hematologic malignancies. In this brief review, we discuss the basic principles of CAR design and clinical studies of CARTs for solid tumors.

Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance.

Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells. These findings suggest that in addition to intrinsic CSCs, non-stem cancer cells may also contribute to the relapse and metastasis of cancer following transformation into CSCs. This review aims to investigate the radiation-induced generation of CSCs, its association with epithelial-mesenchymal transition and its significance with regard to the radioresistance of cancer.

The effects of estrogen and androgen on tear secretion and matrix metalloproteinase-2 expression in lacrimal glands of ovariectomized rats.

PURPOSE: Previous studies have shown that ovariectomy (OVX) induces lacrimal gland regression and that androgens are implicated. This study explored the effects of estrogen and androgen on tear secretion and matrix metalloproteinase 2 (MMP-2) expression in lacrimal glands of ovariectomized rats. METHODS: Sixty-four adult female Wistar rats were randomly divided into three groups (control, sham operated, and OVX). Bilateral OVX was performed in the OVX group. After 5 months, the OVX group was further divided into six subgroups receiving topical ophthalmic or systemic treatment with corn oil vehicle, estradiol, or testosterone for 6 weeks. Schirmer test (SIT), assessment of tear film breakup time (BUT), corneal fluorescein staining, and measurement of estradiol and testosterone levels were performed before OVX and 1, 2, 3, 4, and 5 months after OVX, as well as after 6 weeks of treatment. Lacrimal glands were assessed for MMP-2 mRNA and protein expression. RESULTS: The mean (SD) tear film BUT decreased from 10.53 (0.79) to 9.98 (1.00) seconds (P < 0.01) in the first month after OVX, and the mean (SD) SIT result decreased by 50% from 7.32 (1.61) to 3.39 (1.15) mm (P < 0.01) in the third month after OVX. The mean (SD) corneal fluorescein staining score increased from 0.35 (0.11) to 6.02 (1.34) (P < 0.05) in the fourth month after OVX. The values increased or decreased in parallel with the time course (P < 0.01). In serum, ovariectomy resulted in a mean (SD) decline in estradiol levels from 44.38 (9.78) to 23.00 (3.78) pg/mL (P < 0.01), and the mean (SD) testosterone levels decreased from 2.42 (0.26) to 1.87 (0.15) ng/mL (P < 0.05). The mean (SD) estradiol level was elevated to 35.38 (3.34) pg/mL by systemic estradiol administration for 6 weeks, which also led to further mean (SD) decreases in tear film BUT from 5.28 (0.81) to 3.65 (0.55) seconds (P < 0.01) and in SIT result from 2.19 (1.01) to 1.47 (0.85) mm (P < 0.05), as well as a higher mean (SD) corneal fluorescein staining score from 7.39 (1.34) to 9.89 (1.27) (P < 0.05). However, the mean (SD) testosterone level was increased to 3.53 (0.67) ng/mL by systemic testosterone administration for 6 weeks. As a result, the mean (SD) tear film BUT increased from 5.08 (0.40) to 6.03 (1.48) seconds (P < 0.05), and the mean (SD) SIT result increased from 2.38 (1.20) to 3.66 (1.90) mm (P < 0.05). The mean (SD) corneal fluorescein staining score declined from 7.45 (0.73) to 4.56 (1.21) (P < 0.05). In the nontreated OVX group, the mean (SD) MMP-2 mRNA (0.66 [0.10]) and protein (0.55 [0.13]) expression in lacrimal glands was significantly increased compared with that in the sham-operated group (0.50 [0.09] and 0.40 [0.07], respectively) (P < 0.05). Systemic estradiol administration further increased the mean (SD) MMP-2 mRNA (0.83 [0.10]) and protein (0.69 [0.12]) expression (P < 0.05), while systemic testosterone administration decreased the mean (SD) MMP-2 mRNA (0.12 [0.04]) and protein (0.27 [0.07]) expression (P < 0.01). Topical ophthalmic administration of two sex hormones had no effect on the mean (SD) MMP-2 mRNA (0.59 [0.12] for estradiol and 0.57 [0.14] for testosterone) or protein (0.49 [0.11] for estradiol and 0.46 [0.13] for testosterone) expression (P > 0.05). CONCLUSIONS: Ovariectomy-induced ocular surface impairment may be associated with androgen deficiency. A pathogenetic role for estrogen in dry eye may involve upregulation of MMP-2 expression, while androgen suppresses MMP-2 expression.

Murine corneal stroma cells suppress bone marrow-derived dendritic cells maturation in vitro.

BACKGROUND: Prostaglandin E2 (PGE(2)) is a key modulator of dendritic cells (DCs) function, and cornea-derived transforming growth factor beta 2 (TGF-ß(2)) promotes the generation of phenotypically and functionally immature DCs. Therefore, this study was carried out to investigate whether PGE(2) is involved in the suppressive effect on DCs maturation mediated by corneal stroma cells (CSCs) and whether PGE(2) and TGF-ß(2) have additive effects in this immunosuppressive mechanism. METHODS: Bone marrow-derived DCs (BM-DCs), splenic T cells and CSCs culture supernatant were obtained from mice via various protocols. After that, the level of PGE(2) in CSCs culture supernatant was analyzed by enzyme-linked immunosorbent assay. Then, immature BM-DCs pretreated by E-prostanoid 2 receptor antagonist AH6809 or dimethyl sulfoxide were induced to mature in the presence of lipopolysaccharide, with or without CSCs culture supernatant. In parallel experiments, neutralizing TGF-ß(2) antibody or normal goat IgG was added into the supernatant. Next, the cellular surface markers for DCs maturation, including CD80, CD86, and major histocompatibility complex class II (MHCII), were analyzed by flow cytometry; the capability of stimulating the proliferation of T lymphocytes was evaluated by allogeneic mixed lymphocyte reactions and the function of endocytosis was assessed by fluorescein isothiocyanate-dextran uptake. RESULTS: Higher concentration of PGE(2) was detected in CSCs culture supernatant than in the fresh medium. In addition, compared with control group, after treated with the supernatant in the mature stage, BM-DCs displayed lower expression of CD80, CD86 and MHC II, lower T cell stimulatory capacity and higher endocytosis function. However, after the application of AH6809, BM-DCs partially regained T cell stimulatory capacity and expression of CD86 and MHC II, but partially lost endocytic activity. Moreover, after the application of AH6809 and neutralizing TGF-ß(2) antibody, the result of statistical analysis indicated that there was a statistical difference of interaction in the expression of MHC II and T cell stimulatory capacity. CONCLUSIONS: PGE(2) contributes to the suppressive effect on BM-DCs maturation mediated by CSCs in vitro, and PGE(2) and TGF-ß(2) have additive effects on the immunosuppression of BM-DCs.

Murine corneal stroma cells inhibit LPS-induced dendritic cell maturation partially through TGF-ß2 secretion in vitro.

PURPOSE: The peripheral cornea contains mature and immature resident dendritic cells (DCs) while the central cornea is exclusively equipped with immature DCs. There must be some factors that cause immature DCs. This study investigated whether corneal stroma cells (CSCs) inhibit DC maturation by secreting cytokines. METHODS: The messenger ribonucleic acid (mRNA) and protein level of transforming growth factor beta 2 (TGF-ß(2)) was analyzed using reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Immature DCs were induced to mature in the presence of lipopolysaccharide (LPS) and with concentrations of CSC culture supernatant (containing and not containing neutralizing TGF-ß(2) antibodies). Then, the DC phenotypic and functional maturation were analyzed. RESULTS: CSCs exhibited positive expressions of TGF-ß(2) mRNA and secreted high concentrations of TGF-ß(2) protein. In the presence of LPS, DCs, which were treated with a CSC culture supernatant, displayed reduced expressions of cluster of differentiation 80 (CD80), CD86, and major histocompatibility complex II (MHC II) in a dose-dependent manner. Moreover, treated DCs showed lower T-cell stimulation capacity and a higher endocytosis function. However, these phenotypic and functional modifications were partially reversed after the application of neutralizing TGF-ß(2) antibodies. CONCLUSIONS: This study demonstrates that CSCs can partially inhibit LPS-induced DC maturation through TGF-ß(2) secretion in vitro.

Nasal endoscopy-assisted reconstruction of orbital floor blowout fractures using temporal fascia grafting.

PURPOSE: To present the experience and outcomes of an endoscopy-assisted reconstruction of isolated orbital floor blowout fractures using temporalis fascia grafting. MATERIALS AND METHODS: A retrospective chart review of 32 patients who underwent repair of orbital floor fractures using temporalis fascia grafting from January 1, 2004, through December 1, 2009, was conducted. All procedures were performed through an upper buccal sulcus incision and a transmaxillary endoscopic approach to the orbital floor. The area of displaced bone fragments was limited to 2 cm(2) in all patients in this study. The parameters evaluated before and after surgery included visual acuity, extraocular motility and diplopia, and exophthalmometry. All patients underwent computed tomography before and 6 months after surgery. RESULTS: None of the 32 patients had a postoperative clinical infection or obvious inflammation. Visual acuity was better than or equal to 20/100 in 43% of patients before surgery compared with 76% of patients after surgery. All patients had diplopia before surgery; only 3 had diplopia 6 months after surgery. Enophthalmos was observed in all patients before surgery, and 4 patients still displayed enophthalmos at 6 months after surgery. No sagging of the reconstructed orbital floor was found on computed tomograms 6 months after surgery. CONCLUSIONS: This retrospective study is the first to show that the temporalis fascia is a reliable implant for the repair of orbital floor defects smaller than or equal to 2 cm(2).

Suppressive effect of aqueous humor on lipopolysaccharide-induced dendritic cell maturation.

PURPOSE: The aqueous humor (AH) contains numerous immunosuppressive molecules that contribute to the ocular immune privilege. Here, we mimic an inflammatory environment to analyze the inhibitory effects of the AH on lipopolysaccharide (LPS)-induced maturation of dendritic cells (DC). METHODS: Different concentrations of AH were added to dendritic cell cultures together with LPS. Dendritic cell surface markers CD80, CD86, and MHC-II were assessed by use of flow cytometry. Endocytic capability and mixed lymphocyte reaction were measured as functional maturation. RESULTS: AH inhibited LPS-induced DC maturation, resulting in down-regulated expression of CD80, CD86, MHC-II, enhancement of endocytic capacity, and reduced T cell activation. Neutralizing transforming growth factor beta 2 (TGF-ß(2)) in AH can totally reverse the inhibitory effect. Treatment with prostaglandin E2 (PGE(2)) antagonist alone had no effect on DC maturation. However, blocking of both TGF-ß(2) and PGE(2) in the AH resulted in synergistic suppression of the inhibiting effect of AH. CONCLUSIONS: These results reveal that TGF-ß(2) in the AH is of crucial importance in maintaining DC in the immature state. Further experiments will clarify the immune role of PGE(2) in AH.

[A clinical study on reparation of orbital blowout fracture by bridge hydroxylapatite artificial bone].

OBJECTIVE: To explore a minimally invasive technique with hydroxylapatite artificial bone to repair the orbital blowout fracture. METHODS: Twenty-one cases of orbital blowout fracture from March 2008 to April 2010 were enrolled. And the fractures were repaired with a bridge of hydroxylapatite artificial bone under a nasal endoscope. During a regular 6-month follow-up, anatomic and functional recovery was evaluated. RESULTS: There was neither postoperative visual loss nor infection in all cases. At 3 months post-operation, diplopia vanished completely (n = 17), remained in peripheral vision (n = 2), existed in primary ocular position (n = 2) and the deviation of eyeball (n = 1). At Month 3, diplopia in peripheral vision or in primary position and the deviation of eyeball showed no improvement. Compared with the uninjured side, enophthalmos: ≤ 2 mm (n = 18), > 2 mm (n = 2) and > 4 mm (n = 1). The passive traction test was positive in one case. On computed tomograph (CT) scanning, there was no bone dislocation or slippage in all cases. CONCLUSION: The surgical efficacy is excellent. The technique of combining the advantages of endoscopic sinus approach and hydroxyapatite artificial bone is worth a wider popularization.

Biomechanical considerations: evaluating scleral reinforcement materials for pathological myopia.

OBJECTIVE: Scleral biomechanical weakness and thinness are known to be one of the main factors in the pathogenesis of progressive myopia. Posterior scleral reinforcement surgery remains the rational treatment for pathological myopia. We tested the biomechanical properties of 3 types of scleral reinforcement materials (artificial pericardium, human sclera, and all-dermal matrix) in an attempt to select the ideal material for the reinforcement of pathologic sclera. DESIGN: Experimental study. PARTICIPANTS: Forty-five adult Japanese white rabbits. METHODS: Animals were equally divided into 3 groups. For each group, 1 type of material was surgically implanted at the back of the globe. We harvested samples after 10 months of implantation, tested the elasticity modulus for both reinforced sclera and unreinforced control sclera, and assessed data by t test methods. Statistically significant differences were considered when p < 0.05. RESULTS: Rabbit sclera reinforced by artificial pericardium or human sclera showed significant increases in the elasticity modulus compared with control eyes. However, the rabbit sclera reinforced by all-dermal matrix showed no significant difference in the elasticity modulus compared with normal controls. CONCLUSIONS: The analysis of biomechanical considerations in scleral reinforcement materials presented here is a very helpful method to choose the best materials for treatment of myopia. Of all materials tested, the artificial pericardium and human foreign-body sclera provided the best biomechanical characteristics.

A preliminary study of mesenchymal stem cell-like cells derived from murine corneal stroma.

BACKGROUND: Mesenchymal stem cells can be isolated from various tissues besides bone marrow and can differentiate into cells of three germ layers. Recent studies indicate that some cells in corneal stroma express stem cell markers and can also differentiate into chondrocytes and neurocytes. This study was carried out to investigate whether mesenchymal stem cells reside in the murine corneal stroma. METHODS: Corneas of BALB/c mice were treated with collagenase digestion after the epithelium and endothelium were removed. Then the single cells were harvested and further identified by reverse transcription polymerase chain reaction (RT-PCR). After the immunophenotype of passage 2 corneal stroma-derived cells was analyzed by flow cytometry, attempts were made to differentiate these cells into adipocytes and osteocytes using conditioned medium. Following induction, cells were evaluated by RT-PCR, oil red O and Alizarin Red staining. RESULTS: Isolated single cells were of stromal origin, not of epithelial or endothelial. Passage 2 corneal stroma-derived cells exhibited the spindle-shaped morphology and expressed CD29, CD90, CD105, and CD71; but were negative for CD34 and CD45. In addition, these cells showed the potentiality of differentiating into adipocytes and osteocytes, which was confirmed by RT-PCR and staining. CONCLUSION: This study demonstrates the presence of mesenchymal stem cell-like cells in the murine corneal stroma. Further analysis of these cells will aid elucidation of the mechanisms of some keratopathies, and these cells may be a source for bioengineering of corneal tissue and for cell-based therapeutics.

[Flavectomy of cervical vertebrae in treating cervical spinal canal stenosis].

OBJECTIVE: To investigate the operational method of cervical vertebral flavectomy and its clinical application in the management of cervical canal stenosis. METHODS: From June 1997 to June 2007, 25 patients suffering from cervical spinal canal stenosis caused by obvious flaval ligament hypertrophy were given flavectomy. There were 22 males and 3 females, with an age range of 32 to 68 years (average 54 years). The course of disease was from 3 weeks to 7 years, with an average of 3 years and 7 months. All patients had degenerative cervical canal stenosis; of them, 5 cases had a history of cervical injury 2 to 3 weeks before operation (3 cases of falling injury and 2 cases of traffic accident injury). The X-ray film, CT, and MRI examinations showed that the compression locations were C4-7 in 12 cases, C3-7 in 9 cases, C5-7 in 3 cases, and C6,7 in 1 case. Spinous process and vertebral lamella were exposed by central posterior approach. The insertions of flaval ligaments were cut off at the superior vertebral lamella border, then the starting points of which were cut down from the anterior side of the upper vertebral lamella at their inferior border after lifting up the flaval ligaments. The residual flaval ligaments in front of the vertebral lamella were scraped off by slope rongeur, the dura mater then could be seen to inflate from the intervertebral lamella space, showing the compression having been relieved. Twenty-five cases were all given posterior flavectomy. At 1 week to 3 months after operation, 12 patients received anterior cervical discectomy or vertebral gaining decompression with fusion by bone graft. RESULTS: The time for flavectomy was from 60 to 180 minutes, with an average of 95 minutes. The blood loss during operation was from 90 to 360 mL, with an average of 210 mL. The dura matters were lacerated by knife tips during operation with the cervical vertebrae in hyperflexion in 2 cases. Immediate suture and repair were performed and there were no postoperative cerebrospinal fluid leakage. All the incisions healed by first intension after operation. All of the 25 cases were followed up from 2 to 10 years, with an average of 3 years and 9 months. All patients had no complication of axial symptoms, and no restenosis at their operation site of cervical canal stenosis. The section area ratios of functional spinal canal to spinal cord were 1.12 +/- 0.07 before operation and 2.11 +/- 0.19 at 24 months after operation, showing significant difference (P < 0.05). The range of motion of cervical vertebrae was (39.4 +/- 3.2) degrees before operation and (42.1 +/- 2.9) degrees at 24 months after operation in 13 cases without anterior cervical discectomy fusion, showing no significant difference (P > 0.05); was (34.3 +/- 3.4) degrees before operation and (29.2 +/- 3.6) degrees at 24 months after operation in 12 cases with anterior cervical discectomy fusion, showing significant difference (P < 0.05). The bone graft achieved bony union 3-5 months after operation (average 3.8 months). The Japanese Orthopaedic Association (JOA) scores were 7.9 +/- 2.2 before operation and 15.6 +/- 1.4 at 24 months after operation, showing significant difference (P < 0.05), with an average improvement rate of 86.3%. CONCLUSION: Cervical flavectomy could relieve compression to spinal cord and nerves caused by the flaval ligament hypertrophy without damaging the normal integrality of bony canal, thus avoiding the complication of axial symptoms and so on which are encountered in open-door expansile cervical laminoplasty.

The effect of estrogen and androgen on lacrimal secretion and expression of apoptosis genes in lachrymal gland in ovariectomized rat / 眼科研究

Objective Some scholars considered that dry eye is associated to serum sex level in elder female population.But,how the estrogen and/or androgen play role in dry eye is still in controversy.The goal of the present study was to investigate the effect of estrogen and androgen on lacrimal secretion and expression of apoptosis genes in the lachrymal gland in ovariectomized rat.MethodsSixty-four female Wistar rats were divided into normal contol group,sham operation group and experiment group randomly.Ovariectomy (OVX) was performed in the rats of the experiment group and only partial fat tissue in abdominal cavity was cut in the sham operation group.Lacrimal secretion (Schirmer Ⅰ test),tear film breakup time (BUT) and corneal fluorescence staining examinations were measured in all rats before and 1,2,3,4 and 5 months after the operation.Corn oil,estrogen and androgen were systemically and topically applied 5 months after the operation for six weeks in the OVX experiment group.The experimental rats were sacrificed and the lachrymal glands were obtained for pathohistological examination.The serum estrogen and androgen levels were detected before and 5 months after the operation and before death.The expressions of bax and bcl-2 were detected by immunohistochemistry in the different groups.ResultsThe serum estrogen and androgen levels were significantly decreased after OVX in comaprison with before OVX (P＜0.05).The BUT was obviously shorter in the 1 month after OVX group (P＜0.05).The result of the Schirmer Ⅰ test decreased to 50% in 3 months after OVX (P＜0.01).Corneal fluorescence staining showed positive staining 4 months after OVX and stronger staining 5 months after OVX.In the sixth week after use of androgen,the results of BUT and Schirmer Ⅰ test were considerably decreased but stronger corneal fluorescence straining was seen.However,a complete contrary outcome was found in systemic androgen treatment rats.The expression of bax in lacrimal epithelium cells was increased after estrogen treatment and declinded after androgen treatment.The expression of bcl-2 in lacrimal epithelium cells was declinded after estrogen treatment and increased after androgen treatment.ConclusionIt is supposed that decrease of lacrimal secretion in OVX rats is associated with the decrease of serum androgen.The treatment with androgen can improve lacrimal secretion and decrease the expression of apoptosis gene in lachrymal gland in ovariectomized rat.The apoptosis of lachrymal gland epithelium is one of mechanisms of dry eye.