PDE1B, a potential biomarker associated with tumor microenvironment and clinical prognostic significance in osteosarcoma.

PDE1B had been found to be involved in various diseases, including tumors and non-tumors. However, little was known about the definite role of PDE1B in osteosarcoma. Therefore, we mined public data on osteosarcoma to reveal the prognostic values and immunological roles of the PDE1B gene. Three osteosarcoma-related datasets from online websites were utilized for further data analysis. R 4.3.2 software was utilized to conduct difference analysis, prognostic analysis, gene set enrichment analysis (GSEA), nomogram construction, and immunological evaluations, respectively. Experimental verification of the PDE1B gene in osteosarcoma was conducted by qRT-PCR and western blot, based on the manufacturer's instructions. The PDE1B gene was discovered to be lowly expressed in osteosarcoma, and its low expression was associated with poor OS (all P < 0.05). Experimental verifications by qRT-PCR and western blot results remained consistent (all P < 0.05). Univariate and multivariate Cox regression analyses indicated that the PDE1B gene had independent abilities in predicting OS in the TARGET osteosarcoma dataset (both P < 0.05). GSEA revealed that PDE1B was markedly linked to the calcium, cell cycle, chemokine, JAK STAT, and VEGF pathways. Moreover, PDE1B was found to be markedly associated with immunity (all P < 0.05), and the TIDE algorithm further shed light on that patients with high-PDE1B expression would have a better immune response to immunotherapies than those with low-PDE1B expression, suggesting that the PDE1B gene could prevent immune escape from osteosarcoma. The PDE1B gene was found to be a tumor suppressor gene in osteosarcoma, and its high expression was related to a better OS prognosis, suppressing immune escape from osteosarcoma.

The effect of intraoperative nerve identification technique on distally-based dorsal fasciocutaneous flap for thumb and fingertip reconstruction.

INTRODUCTION: Thumb and fingertip resurfacing continues to be a challenge for hand surgeons, as the treatment varies widely. Being donor nerves in the flap for sensory restoration, the dorsal cutaneous nerves in hand have been widely described in the literature. However, their applications in providing anatomical information to sufficiently harvest the longitudinal axis of a robust flap are usually underestimated. This study reports reconstruction of thumb and fingertip defects with the distally based dorsal fasciocutaneous (DDF) flap and explores the effect of intraoperative nerve identification technique on clinical outcomes. HYPOTHESIS: The nerve identification technique can contribute considerably to the improvement of flap circulation, with less risk of poor venous return. MATERIALS AND METHODS: A retrospective study was conducted in 89 patients who had thumb or fingertip defects treated with the DDF flap from February 2014 to June 2020. Patients were divided into two groups based on whether intraoperative nerve identification technique was used. Flap survival was evaluated. The follow-up was conducted by using smartphone or by face-to-face visit. Time for complete wound healing, time to return to work, hand performance, the total active motion of the joints and static two-point discrimination of flaps were analyzed. RESULTS: The 46 flaps (group A) that underwent intraoperative nerve identification technique had an 8.7% venous congestion rate versus a 27.9% venous congestion rate in the 43 flaps (group B) without using nerve identification technique (p=0.018). The mean follow-up was 11.08 (range 6-26) months. Time for complete wound healing and time to return to work were significantly shorter in group A (p=0.026 and p=0.012). Michigan Hand Outcomes Questionnaire (MHQ) scores were similar between groups. In the face-to-face follow-up, there was no significant difference in the total active motion of the injured fingers and static two-point discrimination between the two groups (p=0.657 and p=0.182). DISCUSSION: The use of nerve identification technique could decrease the odds of postoperative venous congestion in DDF flap for thumb and fingertip reconstruction, and result in improved outcomes in terms of time for complete wound healing and time to return to work. LEVEL OF EVIDENCE: III; retrospective comparative study.

Reverse homodigital dorsoradial flaps for thumb coverage obtained good sensory recovery after a long time follow up.

Reverse homodigital dorsoradial flap (RHDF) of the thumb has become a qualified option for the reconstruction of thumb tissue defects. However, the sensory recovery of the flap in long term is still unknown. Therefore, this study focused on the sensory recovery of RHDFs for the coverage of thumb in hand after a long-term follow-up. From January 2010 to March 2011, 18 patients (14 men and four women) were treated consecutively with an RHDF. All the patients were followed up two times. The pain and cold intolerance of the flap were self-reported by the patients. The sensory recovery of the flap was evaluated using Semmes-Weinstein (SW) monofilament, moving two-point discrimination (M-2PD) and static two-point discrimination (S-2PD) tests. The average times of the first and second follow-up were 39 ± 4 and 88 ± 6 months, respectively. The mean value of SW monofilament sensitivity score and M-2PD at first follow-up was significantly higher than that of the second follow-up and contralateral thumb. The mean value of S-2PD at the second follow-up was significantly lower than that of the first follow-up and higher than that of the contralateral thumb. The cold intolerance severity score (CISS) at the first follow-up was higher than that at the second follow-up. No significant difference was found in terms of the pain between the two follow-ups. RHDFs without nerve coaptation for thumb coverage could obtain good sensory recovery after a long-term follow-up. Abbreviations: RHDF: reverse homodigital dorsoradial flap; CISS: cold intolerance severity score; SW: Semmes-Weinstein monofilament sensitivity score; M-2PD: moving two-point discrimination; S-2PD: static two-point discrimination; VAS: visual analog scale.

Anatomical and Interpositional Bursa Preservation Showed Similar Improved Tendon to Bone Healing Compared With the Bursa Removal in a Rat Rotator Cuff Tear Model.

PURPOSE: To compare the effects of anatomical preservation (AP) and interpositional preservation (IP) of subacromial bursa tissue on tendon-to-bone healing in a rat model of rotator cuff tear. METHODS: In this study, 48 male Sprague-Dawley rats (average weight 283 g) underwent bilateral supraspinatus tendons severed by sharp incision and repaired immediately. The subacromial bursa tissues were completely removed in 16 rats, who served as the control (CON) group. The other 32 rats were randomly divided into 2 groups AP and IP between tendon and bone. Eight rats of each group were sacrificed for bilateral shoulders at 3 and 9 weeks after the operation, including 5 rats for biomechanical tests and 3 for histologic analysis. RESULTS: No significant differences in terms of biomechanical properties were observed among the groups 3 weeks after surgery. At 9 weeks, the maximum load and stiffness of the AP (32.95 ± 6.33 N, P = .029; 12.49 ± 3.17 N/mm, P < .001; respectively) and IP (33.58 ± 8.47 N, P = .015; 11.63 ± 2.84 N/mm, P = .010, respectively) groups were significantly superior to that of the CON group (26.59 ± 4.47 N; 8.42 ± 2.33 N/mm, respectively). More organized collagen and more mature tendon insertion were observed in AP and IP groups at the interface at 9 weeks, which means better tendon-to-bone healing compared with the CON group. CONCLUSIONS: The subacromial bursa plays a positive role in tendon-bone healing. Either anatomical preservation or interpositional preservation between tendon and bone can similarly facilitate the process of healing. CLINICAL RELEVANCE: Considering the additional surgical time and surgical manipulation, preserving the subacromial bursa at the anatomical position seems to be a better way to promote rotator cuff healing.

Further predictive value of lymphovascular invasion explored via supervised deep learning for lymph node metastases in breast cancer.

Lymphovascular invasion, specifically lymph-blood vessel invasion (LBVI), is a risk factor for metastases in breast invasive ductal carcinoma (IDC) and is routinely screened using hematoxylin-eosin histopathological images. However, routine reports only describe whether LBVI is present and does not provide other potential prognostic information of LBVI. This study aims to evaluate the clinical significance of LBVI in 685 IDC cases and explore the added predictive value of LBVI on lymph node metastases (LNM) via supervised deep learning (DL), an expert-experience embedded knowledge transfer learning (EEKT) model in 40 LBVI-positive cases signed by the routine report. Multivariate logistic regression and propensity score matching analysis demonstrated that LBVI (OR 4.203, 95% CI 2.809-6.290, P < 0.001) was a significant risk factor for LNM. Then, the EEKT model trained on 5780 image patches automatically segmented LBVI with a patch-wise Dice similarity coefficient of 0.930 in the test set and output counts, location, and morphometric features of the LBVIs. Some morphometric features were beneficial for further stratification within the 40 LBVI-positive cases. The results showed that LBVI in cases with LNM had a higher short-to-long side ratio of the minimum rectangle (MR) (0.686 vs. 0.480, P = 0.001), LBVI-to-MR area ratio (0.774 vs. 0.702, P = 0.002), and solidity (0.983 vs. 0.934, P = 0.029) compared to LBVI in cases without LNM. The results highlight the potential of DL to assist pathologists in quantifying LBVI and, more importantly, in exploring added prognostic information from LBVI.

Application of three-dimensional visualization technology in phacoemulsification benefits the dry eye symptoms of patients after cataract surgery.

Purpose: To investigate the effects of the three-dimension visualization system on dry eye in patients after cataract phacoemulsification. Methods: Seventy-one patients (104 eyes) were enrolled in this study and assigned to the conventional microscopic group (CM group) or three-dimension group (3D group). Ocular Surface Disease Index, The Schirmer I test (SIt), lipid layer thickness (LLT), noninvasive tear breakup time (NIBUT) and other factors associated with dry eye were recorded before and 1 week and 1 month after surgery. The operation time and intraoperative light intensity (ILI) were also recorded. Results: The ILI in the 3D group was significantly lower than that in the CM group (33% vs. 60%, p < 0.01). There was an interaction (group and time) effect for first NIBUT (NIBUT-F), average NIBUT (NIBUT-Ave), tear meniscus height (TMH) and the score of eye redness (Pinteraction < 0.05). The main effects of group on SIt, LLT, NIBUT-F, NIBUT-Ave and the score of eye redness were significant (Pgroup < 0.05). In the CM group, SIt, LLT, NIBUT-F, NIBUT-Ave, TMH were lower than those of the 3D group, the score of eye redness was higher than that of the 3D group at 1 week and 1 month after surgery (all p < 0.05). The changes in NIBUT-F and NIBUT-Ave between before surgery and 1 week after surgery showed negative correlations with ILI (p < 0.01). Conclusion: Compared with microscopic surgery, the 3D visualization system can provide better tear film stability for patients after cataract surgery.

Intraocular lens power calculation after two different successive corneal refractive surgeries.

Purpose: To report two challenging intraocular lens power calculation cases with patients each underwent different successive corneal refractive surgeries, respectively. Observations: Biometry data, including the Back to Front corneal radii ratio (B/F ratio), were collected by Lenstar, IOL Master, and Pentacam AXL for Case 1 (received radial keratotomy (RK) and photorefractive keratectomy (PRK)) and Case 2 (received RK and laser-assisted in situ keratomileusis (LASIK)). The IOL power calculation was determined by several methods, including Shammas, Haigis-L, and Barrett True-K, which are available in the American Society of Cataract and Refractive Surgery online calculator and Pentacam AXL. The Barrett True-K (no history, post-RK) was more accurate in Case 1 (increased B/F ratio), whereas the Shammas, Haigis-L, and Barrett True-K (no history, post-LASIK/PRK) were more accurate in Case 2 (decreased B/F ratio). Conclusion and importance: The B/F ratio may be a factor to be considered when selecting the IOL power calculation formula for patients who undergo two different corneal refractive surgeries. The further study focusing on this issue should be performed to clarify the results in the future.

A dual meta-learning framework based on idle data for enhancing segmentation of pancreatic cancer.

Automated segmentation of pancreatic cancer is vital for clinical diagnosis and treatment. However, the small size and inconspicuous boundaries limit the segmentation performance, which is further exacerbated for deep learning techniques with the few training samples due to the high threshold of image acquisition and annotation. To alleviate this issue caused by the small-scale dataset, we collect idle multi-parametric MRIs of pancreatic cancer from different studies to construct a relatively large dataset for enhancing the CT pancreatic cancer segmentation. Therefore, we propose a deep learning segmentation model with the dual meta-learning framework for pancreatic cancer. It can integrate the common knowledge of tumors obtained from idle MRIs and salient knowledge from CT images, making high-level features more discriminative. Specifically, the random intermediate modalities between MRIs and CT are first generated to smoothly fill in the gaps in visual appearance and provide rich intermediate representations for ensuing meta-learning scheme. Subsequently, we employ intermediate modalities-based model-agnostic meta-learning to capture and transfer commonalities. At last, a meta-optimizer is utilized to adaptively learn the salient features within CT data, thus alleviating the interference due to internal differences. Comprehensive experimental results demonstrated our method achieved the promising segmentation performance, with a max Dice score of 64.94% on our private dataset, and outperformed state-of-the-art methods on a public pancreatic cancer CT dataset. The proposed method is an effective pancreatic cancer segmentation framework, which can be easily integrated into other segmentation networks and thus promises to be a potential paradigm for alleviating data scarcity challenges using idle data.

Reconstruction of paralyzed arm function in patients with hemiplegia through contralateral seventh cervical nerve cross transfer: a multicenter study and real-world practice guidance.

BACKGROUND: A previous randomized controlled trial showed contralateral seventh cervical nerve (CC7) cross transfer to be safe and effective in restoring the arm function of spastic arm paralysis patients in a specified population. Guidance on indications, safety and expected long-term improvements of the surgery are needed for clinical practice. METHODS: This is a retrospective, multicenter, propensity score-matched cohort study. All patients registered between 2013 and 2019 with unilateral spastic arm paralysis over 1 year who were registered at one of five centers in China and South Korea were included. Patients received CC7 cross transfer or rehabilitation treatment in each center. Primary outcome was the change in the upper-extremity Fugl-Meyer (UEFM) score from baseline to 2-year follow-up; larger increase indicated better functional improvements. FINDINGS: The analysis included 425 eligible patients. After propensity score matching, 336 patients who were 1:1 matched into surgery and rehabilitation groups. Compared to previous trial, patient population was expanded on age (< 12 and > 45 years old), duration of disease (< 5 years) and severity of paralysis (severe disabled patients with UEFM < 20 points). In matched patients, the overall increases of UEFM score from preoperative evaluation to 2-year follow-up were 15.14 in the surgery group and 2.35 in the rehabilitation group (difference, 12.79; 95% CI: 12.02-13.56, p < 0.001). This increase was 16.58 at 3-year and 18.42 at 5-year follow-up compared with the surgery group baseline. Subgroup analysis revealed substantial increase on UEFM score in each subgroup of age, duration of disease, severity of paralysis and cause of injury. No severe complication or disabling sequela were reported in the surgery group. INTERPRETATION: This study showed that CC7 cross transfer can provide effective, safe and stable functional improvements in long-term follow-up, and provided evidences for expanding the indications of the surgery to a wider population of patients with hemiplegia.

Suprascapular nerve injury affects rotator cuff healing: A paired controlled study in a rat model.

PURPOSE: We designed a paired controlled study to investigate the role of the suprascapular nerve (SSN) in rotator cuff healing using a rat tear model, and we hypothesised that rotator cuff healing is impaired in the absence of a healthy SSN. METHODS: Bilateral supraspinatus tenotomy from the great tuberosity was performed for 36 Wistar rats, which was then repaired immediately. A defect on the SSN was made on the right side, and a sham surgery was performed on the SSN at the left side. Twelve rats were sacrificed for biomechanical (six rats) and histological (six rats) testing, evaluated at 3, 6, and 9 weeks after surgery. RESULTS: The bone-tendon junction on the nerve-intact side showed significantly better biomechanical characteristics than the nerve-injured side in terms of maximum load, maximum stress over time, stiffness at 9 weeks, and Young's modulus at 3 and 9 weeks. On the nerve-injured side, significantly smaller fibrocartilage layers and muscle fibres could be obtained over time. In addition, on the nerve-injured side, inferior bone-tendon interface formation was obtained in terms of cell maturity, cell alignment, collagen orientation, and the occurrence of tidemark and Sharpey's fibres through 9 weeks. In addition, neuropeptide Y was secreted in the nerve-intact group at 6 and 9 weeks. CONCLUSION: This study showed the inferior healing of the bone-tendon junction on the nerve-injured side compared with the nerve-intact side, which indicates that the SSN plays an important role in rotator cuff healing. Surgeons should pay more attention to SSN injury when treating patients with rotator cuff tear.

Iris Registration Capsulotomy Marking Versus Manual Marking for Toric Intraocular Lens Alignment in Cataract Surgery.

PURPOSE: To compare the accuracy of toric intraocular lens (IOL) alignment and visual outcomes using femtosecond laser-assisted capsulotomy marking (CM) versus conventional slit lamp-assisted manual marking (MM). DESIGN: Prospective cohort study. METHODS: A total of 57 patients who required cataract surgery and toric IOL implantation (Acrysof SN6AT3-T8) were assigned to the CM group (26 eyes) or the MM group (31 eyes). Uncorrected distant visual acuity (UCDVA), best-corrected distant visual acuity (BCDVA), residual astigmatism (RA), IOL misalignment, and modulation transfer function (area ratio [AR] value) were measured 1 and 3 months after surgery. RESULTS: Postoperative UCDVA (logarithm of minimal angle of resolution [logMAR]) was significantly lower in the CM group than that in the MM group (P < .05). Postoperative RA and IOL misalignment were significantly lower in the CM group than that in the MM group (both P < .05). No significant difference between the groups was observed for BCDVA or AR value (both P > .05). UCDVA (logMAR) was positively correlated with RA (r = 0.339; P < .05) and IOL misalignment (r = 0.317; P < .05) and negatively correlated with the the AR value (r = -0.272; P < .05); RA was positively correlated with IOL misalignment (r = 0.405; P < .05). CONCLUSIONS: The accuracy of the axis alignment was significantly higher in the CM group, which resulted in lower residual astigmatism and better visual outcomes.

[Repair of soft tissue defect of fingers with modified arterialized venous flap].

OBJECTIVE: To summarize the effectiveness of modified arterialized venous flaps in repairing soft tissue defect of fingers. METHODS: Between January 2017 and April 2018, 16 patients with soft defects of fingers were treated. There were 12 males and 4 females, with an average age of 41 years (range, 24-74 years). One case was resulted from resection of cicatricial contracture and 15 cases was caused by mechanical strangulation. The defects located at thumb in 3 cases, index finger in 5 cases, middle finger in 4 cases, ring finger in 2 cases, and little finger in 2 cases; and at the palmar aspect in 4 cases, and dorsal aspect in 12 cases. The size of defect ranged from 3 cm×2 cm to 10 cm×3 cm. All flaps were harvested from the palmar aspect of the ipsilateral forearm. The distal ports of the two veins were ligation. Partial fat was eliminated and the all connecting minute branches between the two veins were ligation under microscope in order to achieve the thorough shunt restriction. Then the flaps were positioned over the recipient site without inversion. The size of flap ranged from 3.5 cm×2.5 cm to 10.5 cm×3.5 cm. All donor sites were directly sutured except that 1 case was recovered with free skin graft. RESULTS: All flaps survived entirely except that 1 case happened vein crisis. Three flaps demonstrated mild-to-moderate venous congestion without any treatment and the swelling of flaps gradually subsided after 1 week. Skin grafting at donor site survived and all incisions healed by first intension. Thirteen patients were followed up 8-16 months (mean, 11 months). The textures and appearances of the flaps were satisfactory. At last follow-up, the mean size of the Semmes-Weinstein (SW) monofilament test of the flaps was 4.01 g (range, 2.83-4.56 g); the mean static two-point discrimination of the flaps was 12 mm (range, 6-20 mm). CONCLUSION: Modified arterialized venous flaps with thoroughly restriction of arteriovenous shunting can offer decreased congestion of venous flaps and improve survival rate. Better effectiveness can be achieved by using this flap to repair soft tissue defect of finger.

Upregulation of HOXB7 promotes proliferation and metastasis of osteosarcoma cells.

Osteosarcoma is the most common primary malignant bone cancer in children and adolescents. Unfortunately, treatment failures are common due to metastasis and chemore-sistance, however, the underlying molecular mechanism remains unclear. Accumulating evidence indicated that the homeobox B7 (HOXB7) gene was associated with the development of cancer. However, the expression and function of HOXB7 in osteosarcoma is still unknown. In the current study, the expression of HOXB7 was upregulated in osteosarcoma tissues and cells compared with paired adjacent non­tumor bone tissues and osteoblastic cells using reverse transcription­quantitative polymer chain reaction and western blotting. HOXB7 knockdown dramatically suppressed cell viability, proliferation, migration and epithelial­mesenchymal transition. Moreover, downregulation of HOXB7 expression significantly inhibited matrix metalloproteinase (MMP)2 and MMP7 protein levels in the MG63 cell line. Therefore, the present results identified that HOXB7 could play a critical role in carcinogenesis, and may serve as a therapeutic target for the treatment of osteosarcoma.

Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery.

PURPOSE: To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS). METHODS: Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated. RESULTS: Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups. CONCLUSIONS: A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.

Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy.

Tumor necrosis factor (TNF) ligand related molecule 1A (TL1A), also termed TNF superfamily member 15 and vascular endothelial growth inhibitor is important for tumorigenicity and autoimmunity. However, the function of TL1A in diabetic retinopathy (DR) remains to be elucidated. The present study established a diabetes mellitus (DM) rat model to investigate TL1A, vascular endothelial growth factor (VEGF), tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) expression levels in the retina, vitreous and serum of rats with DM at different stages (1 month group, 3 month group and 6 month group). The present study determined that TL1A expression levels in the retina and vitreous from the DM 1 month group were significantly lower compared with the control group. However, TL1A levels in the retina and vitreous were significantly increased in advanced stages of DM compared with the control group. Furthermore, the levels of VEGF in the retina and vitreous were significantly higher in the DM groups compared with the control group. The expression levels of TNF­α and IL­1ß in the retina and vitreous were significantly higher in DM 3 month and 6 month groups compared with the control group. It is of note that the expression levels of TL1A were significantly lower in the DM 1 and 3 month groups compared with the control group; however, they were significantly increased in the DM 6 month group compared with the DM 3 month group. The expression levels of VEGF, TNF­α and IL­1ß in blood serum have been observed to exhibit similar expression change dynamics as those of the retina and vitreous. Therefore, these findings suggest that TL1A may be a protective factor of DR, and may provide a rationale for the development of novel therapeutic strategies to treat DR.

Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats.

PURPOSE: We aimed to evaluate the effect of IL-10 gene transfection on endothelial progenitor cells (EPCs) under inflammatory conditions, and explore the therapeutic potential of IL-10-transfected EPC transplantation on nonproliferative diabetic retinopathy (NPDR). METHODS: Lentivirus vectors encoding IL-10 were constructed and introduced into EPCs isolated from rat bone marrow. After exposure to recombinant rat TNF-α, abilities of nontransfected EPCs (non-EPCs) and EPCs transfected with normal control lentivirus (EPCs-GFP) or IL-10 expressing lentivirus (EPCs-IL-10-GFP) were assessed, including migration, adhesion, and tube formation. IL-10 production by EPCs-IL-10-GFP was determined by ELISA. Following 12 weeks after establishment of diabetes, diabetic rats were randomly injected with non-EPCs, EPCs-GFP, or EPCs-IL-10-GFP via tail vein. Expression of inflammatory factors and factors associated with nuclear factor-kappa B (NF-kB) signal pathway, retinal histological analysis, and retinal vascular permeability were assessed 2 weeks after transplantation. RESULTS: The detrimental effects of TNF-ɑ on the abilities of EPCs were significantly attenuated in EPCs-IL-10-GFP compared with non-EPCs and EPCs-GFP. The concentration of IL-10 in the EPCs-IL-10-GFP group was significantly higher than the non-EPCs and EPCs-GFP groups. Additionally, transplantation of EPCs-IL-10-GFP significantly inhibited inflammatory factors expression and activation of NF-kB signal pathway, improved retinal histological changes, and attenuated retinal vascular permeability. CONCLUSION: In conclusion, transplantation of IL-10-transfected EPCs significantly improved EPCs-mediated retinal vascular repair and subsequently suppressed NPDR progression. This was associated with inflammation suppression, at least partly via inhibiting the NF-kB signal pathway. Transplantation of IL-10-transfected EPCs may be a new strategy for treatment of NPDR.

TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies.

Interleukin-10 overexpression improves the function of endothelial progenitor cells stimulated with TNF-α through the activation of the STAT3 signaling pathway.

Lentivirus vector-interleukin-10 green fluorescent protein (LV-IL-10-GFP) was transfected into endothelial progenitor cells (EPCs) in the present study. The aim was to detect the function of IL­10­modified EPCs and analyze the molecular mechanism. EPCs were cultured and identified by fluorescent labeling with the von Willebrand factor antibody, vascular endothelial growth factor (VEGF) receptor, Ulex europaeus agglutinin-1 and acetylated low­density lipoprotein. Subsequently, EPCs were transfected with LV-IL-10-GFP and lentivirus vector­noncontain­GFP as the control group. Enzyme­linked immunosorbent assay (ELISA) was used to detect the concentrations of cytokines in the supernatant with or without tumor necrosis factor­α (TNF­α). All types of cells were assessed by a tube formation assay, adhesion assay and migration assay induced with or without TNF­α. Cell cycle was assessed by flow cytometry. Western blot analysis was applied to detect the expression of proteins in the cells. ELISA analysis showed that the levels of TNF­α and IL­8 in the supernatant without TNF­α significantly decreased in EPC­LV­IL­10­GFP (P<0.05 for all). By contrast, the levels of IL­10 and VEGF were contrasting in association with these. The concentrations of cytokines in the supernatant with TNF­α were consistent to the supernatant without TNF­α. There was no statistically significant difference in the average number of EPCs undergoing migration, adhesion, total length and cell growth among the EPC, EPC­LV­IL­10­GFP and EPC­LV­NC­GFP groups without TNF­α. Further study showed that EPC­LV­IL­10­GFP with TNF­α significantly enhanced EPC migration, adhesion and promoted tube formation (P<0.05 for all). Western blot analysis revealed that the expression of VEGF, matrix metallopeptidase­9 and phosphorylated­signal transducer and activator of transcription 3 (p­STAT3) significantly increased in the EPC­LV­IL­10­GFP group. Conversely, STAT­3 expression decreased in the EPC­LV­IL­10­GFP group. The present study suggested that overexpression of IL­10 had no effect on migration, adhesion, tubule formation and cell growth of EPCs without TNF­α. Furthermore, in EPCs stimulated with TNF­α, the overexpression of IL­10 improved EPC function, including migration, adhesion and tubule formation by activating the STAT3 signal pathway.

[Verumontanum hypertrophy in chronic prostatitis].

OBJECTIVE: To investigate the relationship of verumontanum hypertrophy with chronic prostatitis. METHODS: Fifty-two patients with chronic prostatitis underwent cystourethroscopy for comparing the size of the verumontanum before and after treatment. RESULTS: Before treatment, all the patients showed different degrees verumontanum hypertrophy, of whom 50 were treated by conventional drug therapy, and the other 2 with voiding dysfunction by drug therapy combined with transurethral resection. Cystourethroscopy revealed significantly decreased size of the verumontanum in 44 of the patients after treatment (P < 0.05). CONCLUSION: Patients with chronic prostatitis often have verumontanum hypertrophy, which could be an indicator of the effect of treatment.