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.

Microfracture Lateral to the Greater Tuberosity of the Humerus Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Model.

BACKGROUND: Microfracture at the rotator cuff insertion is an established surgical marrow-stimulation technique for enhancing rotator cuff healing. However, the effect of lateralized or medialized microfracture on the insertion is unknown. PURPOSE: To compare the biomechanical and histologic effects of microfracture at 3 different regions for rotator cuff repair in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 72 Sprague-Dawley rats with bilateral supraspinatus tendon insertion detachment were allocated into 4 groups with 4 different interventions: no microfracture at the humeral head as a control group (Con), traditional microfracture at the footprint area (MFA), and medialized microfracture to the footprint area (MMFA) on the articular surface of the humerus or lateralized microfracture to the footprint area at the greater tuberosity (LMFA). All underwent immediate repair. Tendon-to-bone healing was assessed by biomechanical and histologic tests 4 and 8 weeks postoperation. RESULTS: At 4 weeks, the LMFA group showed a significantly superior failure load compared with the other groups (all P < .05). The LMFA and MFA groups showed significantly superior stiffness compared with the Con and MMFA groups (all P < .01). At 8 weeks, superior failure load and stiffness were observed in the LMFA group compared with the control group (all P < .05). Histologic examination revealed that the LMFA group had superior collagen composition and tendon-to-bone maturation at the interface at 4 and 8 weeks compared with the Con group (all P < .05). CONCLUSION: Lateralized microfracture at the greater tuberosity improved the histologic quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in a rat model. CLINICAL RELEVANCE: Microfracture lateral to the footprint area might be a better way to enhance rotator cuff healing clinically.

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.

Protection of hatchlings against coccidiosis by maternal antibodies to four recombinant proteins of Eimeria tenella, Eimeria acervulina and Eimeria maxima.

Maternally derived IgG antibodies to protective Eimeria antigens have great potential to control chicken coccidiosis and multivalent vaccines are more practical to resist against co-infection with several species of Eimeria under natural conditions. In this study, five good protective antigens of Eimeria species were combined into two combinations based on previous studies, namely C1(EtROPK-Eten5-A, EtGAM22, Ea3-1E and EmGAM56) and C2(EtM2AP and EtGAM22, Ea3-1E and EmGAM56). Then, five antigens were expressed in the Escherichia coli system and purified to inoculate breeding hens. After three times immunization, the specific antibodies could sustain for 11 and 10 weeks in hens' plasma and egg yolk, respectively. Moreover, maternally derived antibodies against recombinant proteins could retain for 14 days in hatchlings' serum. Then, protective efficacies of specific antibodies on hatchlings against mixed infection of E. tenella, E. acervulina and E. maxima were evaluated. The results showed that the hatchlings of the immunized hens had a higher survival rate on day 7 of hatching. Moreover, body weight gains within the hatchlings of immunized hens were higher than those of unvaccinated hens on 7 days (C1: p = 0.0744; C2: p = 0.4020) and 14 days (p < 0.0001). Moreover, hatchlings from vaccinated hens showed significantly alleviated lesion scores in the small intestine and duodenum at day 7 (p < 0.01) and day 14 (C1: p < 0.05). Particularly, the number of oocyst excretion from hatchlings of immunized hens was significantly reduced at day 7 (p < 0.0001) and day 14 (p < 0.0001). Our findings suggest that the maternal immunization with multivalent recombinant vaccines has the potential to be transmission blocking vaccines against mixed infection of Eimeria.

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.

Endoplasmic Reticulum Stress Regulates Scleral Remodeling in a Guinea Pig Model of Form-Deprivation Myopia.

PURPOSE: This study aimed to investigate the role of endoplasmic reticulum (ER) stress in scleral remodeling in a guinea pig model of form-deprivation myopia (FDM). METHODS: Guinea pigs were form deprived to induce myopia. ER ultrastructural changes in the sclera were examined by transmission electron microscopy (TEM). The protein levels of ER stress chaperones, including GRP78, CHOP, and calreticulin (CRT), were analyzed by western blotting at 24 hours, 1 week, and 4 weeks of FD. Scleral fibroblasts from guinea pigs were cultured and exposed to the ER stress inducer tunicamycin (TM) or the ER stress inhibitor 4-phenylbutyric acid (4-PBA). CRT was knocked down by lentivirus-mediated CRT shRNA transfection. The expression levels of GRP78, CHOP, TGF-ß1, and COL1A1 were analyzed by qRT-PCR or western blotting. RESULTS: The sclera of FDM eyes exhibited swollen and distended ER at 4 weeks, as well as significantly increased protein expression of GRP78 and CRT at 1 week and 4 weeks, compared to the sclera of the control eyes. In vitro, TM induced ER stress in scleral fibroblasts, which was suppressed by 4-PBA. The mRNA expression of TGF-ß1 and COL1A1 was upregulated after TM stimulation for 24 hours, but downregulated for 48 hours. Additionally, change of TGF-ß1 and COL1A1 transcription induced by TM was suppressed by CRT knockdown. CONCLUSIONS: ER stress was an important modulator which could influence the expression of the scleral collagen. CRT might be a new target for the intervention of the FDM scleral remodeling process.

[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.

Comparative effects of implanted electrodes with differing contact patterns on peripheral nerve regeneration and functional recovery.

Electrical stimulation could enhance nerve regeneration and functional recovery. The objective of this study was to evaluate the regenerative effects of implanted electrodes with different contacts in resected sciatic nerve. Sciatic nerve resection and microsurgical repair models were established and randomly divided into four groups (point contact, 1/4 circle contact; whole-circle contact; no electrodes as control). Electrical stimulation was performed and electrophysiological, morphological and histological exams (of the sciatic nerve and muscle) were conducted at 4 and 10 weeks post-implantation. Point and 1/4 circle contact groups showed significantly higher scores in the sciatic functional index (SFI), increased amplitude of compound muscle action potential (AMP) and motor nerve conduction velocity (MNCV) compared to the control group at both 4 and 10 weeks post-implantation. Point and 1/4 circle contact morphologically promoted sciatic nerve regeneration and reduced muscular atrophy with less mechanical injury to the nerve trunk observed compared with the whole-circle contact group at both 4 and 10 weeks post-implantation. Electrodes with point and 1/4 circle contacts represented an alternatively portable and effective method of electrical stimulation to facilitate injured sciatic nerve regeneration and reduce subsequent muscular atrophy, which might offer a promising approach for treating peripheral nerve injuries.

Contralateral C7 to C7 nerve root transfer in reconstruction for treatment of total brachial plexus palsy: anatomical basis and preliminary clinical results.

OBJECTIVEContralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.METHODSThis was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.RESULTSIn the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.CONCLUSIONSThe C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.

The Role of the RhoA/ROCK Signaling Pathway in Mechanical Strain-Induced Scleral Myofibroblast Differentiation.

Purpose: Biomechanical properties changes and α-smooth muscle actin (α-SMA) overexpression are involved in myopia scleral remodeling. However, interactions between altered tissue biomechanics and cellular signaling that sustain scleral remodeling have not been well defined. We determine the mechanisms of mechanotransduction in the regulation of α-SMA expression during myopia scleral remodeling. Methods: Guinea pigs were used to establish a form-deprivation myopia (FDM) model. Protein profiles in myopic sclera were examined using tandem mass spectrometry. Ras homolog gene family member A (RhoA) and α-SMA expressions were confirmed using quantitative (q) RT-PCR and Western blotting. Scleral fibroblasts were cultured and subjected to 4% cyclic strain. Levels of RhoA, rho-associated protein kinase-2 (ROCK2), myocardin-related transcription factor-A (MRTF-A), serum response factor (SRF), and α-SMA were determined by qRT-PCR and Western blotting in groups with or without the RhoA siRNA or ROCK inhibitor Y27632. MRTF-A and α-SMA were evaluated by confocal immunofluorescent microscopy and myofibroblasts were enumerated using flow cytometry. Results: mRNA and protein levels of RhoA and α-SMA were significantly increased in the FDM eyes after 4 weeks of form-deprivation treatment. The 4% static strain increased expressions of RhoA, ROCK2, MRTF-A, SRF, and α-SMA as well as nuclear translocalization of MRTF-A in scleral fibroblasts compared to those without strain stimulation. Additionally, the percentage of myofibroblasts increased after strain stimulation. Conversely, inhibition of RhoA or ROCK2 reversed the strain-induced α-SMA expression and myofibroblast ratio. Conclusions: Mechanical strain activated RhoA signaling and scleral myofibroblast differentiation. Strain also mediated myofibroblast differentiation via the RhoA/ROCK2-MRTF-A/SRF pathway. These findings provided evidence for a mechanical strain-induced RhoA/ROCK2 pathway that may contribute to myopia scleral remodeling.

Crosslinking Enzyme Lysyl Oxidase Modulates Scleral Remodeling in Form-Deprivation Myopia.

PURPOSE: Scleral remodeling causes the excessive ocular elongation that underlies myopia. Lysyl oxidase (LOX), a copper-containing amine oxidase, can catalyze collagen and elastin crosslinking. The purpose of this study was to investigate the role of LOX in scleral remodeling in form-deprivation myopia (FDM). METHODS: Seventy-five guinea pigs were randomly divided into five groups as follows: a normal control group, an FDM group, an FDM plus ß-aminopropionitrile (BAPN) group, an FDM plus TGF-ß1 (TGF-ß1) group, and an FDM plus vehicle group. A translucent diffuser was used to induce FDM, and intravitreal injection was used to administer BAPN, TGF-ß1 or vehicle. The scleral LOX and collagen gene and protein levels and the posterior scleral ultrastructure and biomechanics were measured. RESULTS: In the FDM group, both the scleral LOX and collagen gene and protein levels were significantly lower than those in the control eyes. The collagen fibril diameters were significantly decreased in the FDM group compared with the diameters in the control group. A significant decrease in LOX gene and protein expression was observed after BAPN injection, and an increase was observed after TGF-ß1 treatment compared with the levels in the FDM group. Additionally, the scleral collagen fibrils were significantly decreased in the BAPN-treated eyes but increased in the TGF-ß1-treated eyes compared with the FDM eyes. The ultimate stress and Young's modulus of the sclera were lowest in the BAPN group, followed by the FDM group and the TGF-ß1 group. The ultimate strain (%) of the sclera was lowest in the TGF-ß1 group, followed by the FDM group and the BAPN group. CONCLUSION: LOX expression was significantly lowered in myopic sclera. Modulating LOX expression induced a change in both the scleral collagen fibril diameter and the scleral biomechanics. Therefore, LOX may play a key role in the myopia scleral remodeling procedure.

Interaction between Corneal and Internal Ocular Aberrations Induced by Orthokeratology and Its Influential Factors.

PURPOSE: To investigate the interaction between corneal, internal, and total wavefront aberrations (WAs) and their influential factors during orthokeratology (OK) treatment in Chinese adolescents. METHODS: Thirty teenagers (n = 30 eyes) were enrolled in the study; spherical equivalent refraction (SE), corneal curvature radius (CCR), central corneal thickness (CCT), WAs, and the difference in limbal transverse diameter and OK lens diameter (ΔLLD) were detected before and after one-month OK treatment. Every component of WAs was measured simultaneously by iTrace aberrometer. The influential factors of OK-induced WAs were analyzed. RESULTS: SE and CCT decreased while CCR increased significantly (P < 0.01). Higher-order aberrations (HOAs), Spherical aberrations (SAs), and coma increased significantly (P < 0.01). Corneal horizontal coma (Z31-C) and corneal spherical aberrations (Z40-C) increased (P < 0.01). The HOAs, coma, SAs, Z31-C, Z31-T, Z40-C, and Z40-T were positively correlated with SE and CCR (P < 0.01). Z3-1-C showed negative correlations with (ΔLLD) and positive correlations with SE (P < 0.05). CONCLUSIONS: The increase in OK-induced HOAs is mainly attributed to Z31 and Z40 of cornea. Z3-1 in the internal component showed a compensative effect on the corneal vertical coma. The degree of myopic correction and increase in CCR may be the essential influential factors of the increase in Z31 and Z40. The appropriate size of the OK lens may be helpful to decrease OK-induced vertical coma.