Well-dispersed platelet lysate entrapped nanoparticles incorporate with injectable PDLLA-PEG-PDLLA triblock for preferable cartilage engineering application.

Platelet lysate (PL) as a cost-effective cocktail of growth factors is an emerging ingredient in regenerative medicine, especially in cartilage tissue engineering. However, most studies fail to pay attention to PL's intrinsic characteristics and incorporate it directly with scaffolds or hydrogels by simple mixture. Currently, the particle size distribution of PL was determined to be scattered. Directly introducing PL into a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel disturbed its sol-gel transition. Electrostatic self-assembly heparin (Hep) and ε-poly-l-lysine (EPL) nanoparticles (NPs) were fabricated to improve the dispersity of PL. Such PL-NPs-incorporated PLEL gels retained the initial gelling capacity and showed a long-term PL-releasing ability. Moreover, the PL-loaded composite hydrogels inhibited the inflammatory response and dedifferentiation of IL-1ß-induced chondrocytes. For in vivo applications, the PLEL@PL-NPs system ameliorated the early cartilage degeneration and promoted cartilage repair in the late stage of osteoarthritis. RNA sequencing analysis indicated that PL's protective effects might be associated with modulating hyaluronan synthase 1 (HAS-1) expression. Taken together, these results suggest that well-dispersed PL by Hep/EPL NPs is a preferable approach for its incorporation into hydrogels and the constructed PLEL@PL-NPs system is a promising cell-free and stepwise treatment option for cartilage tissue engineering.

A free-standing multilayer film as a novel delivery carrier of platelet lysates for potential wound-dressing applications.

Great efforts have been made to develop suitable bioactive constructs that release growth factors (GFs) in a controlled manner for tissue-regeneration applications. Platelet lysates (PLs) are an affordable source of multiple GFs and other proteins, and show great potential in the wound-healing process. Herein, poly-l-lysine (PLL) and hyaluronic acid (HA) were applied to build free-standing polyelectrolyte multilayer films (PEMs) using the PH-amplified layer-by-layer self-assembly method. Molecular simulations were performed, which showed that in the end layer of PEMs, HA was more attractive to PLs than was PLL. The HA/PLL films constructed with or without 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) cross-linking both absorbed PLs successfully, exhibiting high hydrophilicity and GF absorptivity. The release profile of the EDC30 film lasted up to 2 weeks, and PL-loaded films supported cell proliferation, adhesion, migration, and angiogenesis in vitro. Moreover, due to sustained delivery of PLs, the membranes (especially the crosslinked film) helped to promote granulation-tissue formation, collagen deposition, and neovascularization in the region of the defect, resulting in rapid re-epithelialization and regeneration of skin. Mechanistically, the beneficial effects of a PL-loaded PEM coating might be related to activation of the hypoxia-inducible factor-1(Hif-1α)/vascular endothelial growth factor (VEGF) axis. As an off-the-shelf and cell-free treatment option, these biomimetic multilayers have great potential for use in the fabrication of devices that allow stable incorporation of PLs, thereby exerting synergistic effects for efficient wound healing.

Comparison of fracture risk using different supplemental doses of vitamin D, calcium or their combination: a network meta-analysis of randomised controlled trials.

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624.

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports.

BACKGROUND: Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug's AEs (which may change during a drug's life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O'Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. METHODS: In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles' references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. RESULTS: One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing's syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. CONCLUSIONS: The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

Association of osteoarthritis and circulating adiponectin levels: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and osteoarthritis (OA). METHOD: Multiple databases were searched to estimate the high quality of studies relevant to adiponectin and OA. We extracted the data from the eligible studies and included them in the meta-analysis using a random effects model. Subgroup analysis and meta-regression were further performed to explore the potential sources of heterogeneity. RESULTS: Ten articles consisting of thirteen case-control studies that contained a combined total of 1255 subjects. Our results revealed that the OA patients displayed higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11-0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians (P = 0.037). Moreover, the meta-regression analysis suggested that the sample size (P = 0.03) and nationality (p = 0.01) could account for a part of heterogeneity in our study. CONCLUSION: Taken together, the current study indicated that the adiponectin expression levels were higher in the OA patients than in the healthy controls and might be associated with OA prevalence.

[Association of Ureaplasma urealyticum with the types of antisperm antibody in infertile men].

OBJECTIVE: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection. METHODS: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects. RESULTS: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ï¼»350/662ï¼½ vs 16.00% ï¼»4/25ï¼½, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05). CONCLUSIONS: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.

Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Spinal cord injury (SCI) is a severe neurological disease with few efficacious drugs. Autophagy is a cellular process to confront with stress after SCI and considered to be a therapeutic target of SCI. In this study, we investigated the therapeutic effect of metformin on functional recovery after SCI and its underlying mechanism of autophagy regulation. Using a rat model of traumatic SCI, we found improved function recovery which was paralleled by a reduction of apoptosis after metformin treatment. We further examined autophagy via detecting autophagosomes by transmission electron microscopy and immunofluorescence, as well as autophagy markers by western blot in each groups. The results showed that the number of autophagosomes and expression of autophagy markers such as LC3 and beclin1 were increased in SCI group, while autophagy substrate protein p62 as well as ubiquitinated proteins were found to accumulate in SCI group, indicating an impaired autophagy flux in SCI. But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and functional recovery effect of metformin on SCI, which suggested that the protective effect of metformin on SCI was through autophagy flux stimulation. Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation. Together, these results illustrated that metformin improved functional recovery effect through autophagy flux stimulation and implied metformin to be a potential drug for SCI therapy.

[Sperm chromatin structure assay versus sperm chromatin dispersion test in detecting sperm DNA integrity and correlation of sperm DNA fragmentation with semen parameters].

OBJECTIVE: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality. METHODS: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the age of the patients. RESULTS: A significant consistency was found in the SDF index (DFI) between the two methods (P<0.01). The DFI was correlated negatively with sperm motility, the percentage of progressively motile sperm, and that of morphologically normal sperm (P <0.01), but positively with the teratozoospermia index (P <0.01 in SCSA and P <0.05 in SCD). The DFI measured by SCSA showed a significantly positive correlation with the patients' age (P <0.01), but not that obtained by SCD. CONCLUSIONS: The results of both SCSA and SCD play an important role in predicting sperm quality. As a clinical index, the DFI has a predictive value for male infertility. However, the results of different detecting methods vary widely, which calls for further studies on their standardization.

[Relationship of sperm morphology with the outcomes of in vitro fertilization and embryo transfer].

OBJECTIVE: To study the application value of normal sperm morphology on the outcomes of classic in vitro fertilization and embryo transfer (IVF-ET). METHODS: This study included 659 infertile couples admitted to our center for IVF-ET. Based on the percentage of morphologically normal sperm (MNS), we divided the patients into groups A (n = 112, MNS < 2%), B (n = 180, MNS > or = 2 - < 4%), C (n = 74, MNS > or = 4 - < 5%), and D (n = 293, MNS > or = 5%), and compared the rates of fertilization, normal fertilization, embryos obtained, biochemical pregnancy, clinical pregnancy, implantation, and live birth among different groups. RESULTS: The mean fertilization rate was significantly higher in groups C (71.90%) and D (72.89%) than in A (57.97%) and B (63.29%) (P < 0.05), with no remarkable differences either between A and B (P > 0.05) or between C and D (P > 0.05). The normal fertilization rate was also significantly higher in group D (57.16%) than in A (46.52%) and B (50.89%) (both P < 0.05) as well as in C (54.67%) than in A (P < 0.05). The rate of embryos obtained, too, was markedly higher in group D (55.62%) than in B (45.75%) (P < 0.05), but none with remarkable difference from other groups (all P > 0.05). There were no statistically significant differences among the four groups in the rates of biochemical pregnancy, clinical pregnancy, implantation, abortion, and live birth (all P > 0.05). CONCLUSION: The rate of MNS had some influence on IVF-ET, and 5% MNS exhibited a higher value than 4% MNS in predicting the outcomes of IVF.

[Analysis of GJB2 gene and mitochondrial DNA A1555G mutations in 16 families with non-syndromic hearing loss].

OBJECTIVE: To screen for genetic mutations in families featuring non-syndromic hearing loss. METHODS: Sixteen families with non-syndromic hearing loss were interviewed to identify medical histories by a questionnaire. Audiological and neurological examinations were conducted for all families. Coding regions of GJB2 and 12S rRNA genes were amplified and sequenced. RESULTS: Of the 17 patients with sensorineural hearing loss, 3 were homozygous mutation for GJB2 235 delC, 1 was 235 delC heterozygous mutation, 1 was 235 delC+299_300 delAT compound heterozygous mutation, and 6 were 79G>A+341G>A heterozygosis in cis mutation. No 1555A>G mutation of mitochondrial DNA (mtDNA) was found in the 16 families. CONCLUSION: The incidence of mtDNA 12S rRNA 1555A>G mutation in Jiangsu province may be lower than the average across China. Mutations of GJB2 genes may account for as much as 64.7% of non-syndromic hearing loss in this study. Screening for such mutations and genetic counseling may play an important role in the prevention of hereditary hearing loss.

Effects of Tai Chi versus Proprioception Exercise Program on Neuromuscular Function of the Ankle in Elderly People: A Randomized Controlled Trial.

Background. Tai Chi is a traditional Chinese medicine exercise used for improving neuromuscular function. This study aimed to investigate the effects of Tai Chi versus proprioception exercise program on neuromuscular function of the ankle in elderly people. Methods. Sixty elderly subjects were randomly allocated into three groups of 20 subjects per group. For 16 consecutive weeks, subjects participated in Tai Chi, proprioception exercise, or no structured exercise. Primary outcome measures included joint position sense and muscle strength of ankle. Subjects completed a satisfaction questionnaire upon study completion in Tai Chi and proprioception groups. Results. (1) Both Tai Chi group and proprioception exercise group were significantly better than control group in joint position sense of ankle, and there were no significant differences in joint position sense of ankle between TC group and PE group. (2) There were no significant differences in muscle strength of ankle among groups. (3) Subjects expressed more satisfaction with Tai Chi than with proprioception exercise program. Conclusions. None of the outcome measures on neuromuscular function at the ankle showed significant change posttraining in the two structured exercise groups. However, the subjects expressed more interest in and satisfaction with Tai Chi than proprioception exercise.