Extracellular vesicles secreted from mesenchymal stem cells ameliorate renal ischemia reperfusion injury by delivering miR-100-5p targeting FKBP5/AKT axis.

The incidence of acute kidney injury (AKI) due to ischemia-reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Comparison of Arthroscopic-Assisted Percutaneous Internal Fixation With a Modified Reducer Versus Open Reduction and Internal Fixation for Schatzker Type II and III Tibial Plateau Fractures.

Background: Tibial plateau fractures require anatomical reduction and stable fixation to achieve satisfactory results. In addition, addressing any related injuries is of paramount importance. Arthroscopic reduction and internal fixation (ARIF) has been promoted as a possible technique to treat tibial plateau fractures. Purpose: To compare the effectiveness of ARIF with this modified reducer and open reduction and internal fixation (ORIF) for Schatzker types II and III tibial plateau fractures. Study Design: Cohort study; Level of evidence, 3. Methods: We retrospectively reviewed 68 patients who were treated for Schatzker type II or III tibial plateau fractures between August 1, 2014, and October 31, 2018. Patients were categorized into the ARIF (n = 33) and ORIF groups (n = 35). The groups were compared regarding intra-articular injuries, duration of hospital stay, complications, and clinical outcomes-including the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) score, and range of motion (ROM). The paired t test was used to compare preoperative and postoperative data, and the chi-square test was used to compare the IKDC and HSS scores. Results: The median follow-up period was 36 months (26-40 months). Additional intra-articular lesions were found in 29 patients-21 in the ARIF group and 8 in the ORIF group (P = .02). A significant difference was observed in the duration of hospital stay-3.58 ± 1.46 days for the ARIF group and 4.57 ± 1.12 days for the ORIF group (t = -3.169; P = .002). All fractures healed within 3 months after surgery. The complication rate for all patients was 11%, with no significant difference between the ARIF and ORIF groups (t = 1.244; P = .265). At the final follow-up, there were no significant differences between the 2 groups in the IKDC score, HSS score, and ROM (P > .05 for all). Conclusion: ARIF with a modified reducer was found to be an effective, reliable, and safe procedure for the treatment of Schatzker types II and III tibial plateau fractures. Both ARIF and ORIF provided equally good results, while ARIF offered a more precise evaluation and reduced the duration of hospital stay.

[Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring].

OBJECTIVE: To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy. METHODS: From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria). RESULTS: All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05). CONCLUSION: The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

How Far Can We Push the Rigid Oligomers/Polymers toward Ferroelectric Nematic Liquid Crystals?

The emerging ferroelectric nematic (NF) liquid crystal is a novel 3D-ordered liquid exhibiting macroscopic electric polarization. The combination of the ultrahigh dielectric constant, strong nonlinear optical signal, and high sensitivity to the electric field makes NF materials promising for the development of advanced liquid crystal electroopic devices. Previously, all studies focused on the rod-shaped small molecules with limited length (l) range and dipole moment (µ) values. Here, through the precision synthesis, we extend the aromatic rod-shaped mesogen to oligomer/polymer (repeat unit up to 12 with monodisperse molecular-weight dispersion) and increase the µ value over 30 Debye (D). The NF phase has a widespread existence far beyond our expectation and could be observed in all the oligomer/polymer length range. Notably, the NF phase experiences a nontrivial evolution pathway with the traditional apolar nematic phase completely suppressed, i.e., the NF phase nucleates directly from the isotropic liquid phase. The discovery of thte ferroelectric packing of oligomer/polymer rods not only offers the concept of extending the NF state to oligomers/polymers but also provides some previously overlooked insights in oxybenzoate-based liquid crystal polymer materials.

Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. METHODS: Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immune-related genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines. RESULTS: A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRlncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient. CONCLUSION: Our results demonstrate some sIRlncRs with remark clinical relevance show the latent monitoring and prognosis values for ccRCC patients and may provide new insight in immunological researches and treatment strategies of ccRCC patients.

[Repair effect of bFGF combined with bone marrow mesenchymal stem cells on spinal cord injury in rats].

OBJECTIVE: To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism. METHODS: SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale. RESULTS: The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (P<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (P<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(P<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(P<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(P<0.05). CONCLUSIONS: The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.

Association Between Changes in Serum 5-Hydroxy-Tryptamine Concentrations and Improvement in Clinical Symptoms in Primary Premature Ejaculation with Paroxetine Treatment.

BACKGROUND: This study aimed to investigate the association between changes in serum 5-hydroxy tryptamine (5-HT) concentrations and improvement in clinical symptoms in primary premature ejaculation with paroxetine treatment. MATERIAL AND METHODS: A total of 142 men aged 18-65 years with a history of lifelong premature ejaculation and an intravaginal ejaculation latency time (IELT) <120 s were included in this study. Patients were divided into 3 groups according to IELT: IELT ≤30 s (group A), (IELT >30 s and ≤60 s (group B), and IELT >60 s and <120 s (group C). Patients in the 3 groups were administered paroxetine hydrochloride 20 mg/d for 8 weeks. Blood samples were obtained from the candidates in the screening period and after 8 weeks of treatment. Plasma 5-hydroxy-tryptamine (5-HT) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Reliable data from 125 patients were obtained. There were 41 patients in group A, 40 in group B, and 44 in Group C. IELT and serum 5-HT concentrations were significantly improved in the 3 groups after treatment (all P<0.001). The mean change and fold increase in IELT and the mean change in serum 5-HT concentrations in group A were significantly higher than those in groups B and C (all P<0.001). The mean change and fold increase in IELT and the mean change in serum 5-HT concentrations in group B were significantly higher than those in group C (all P<0.001). Significantly more patients in group A achieved clinical benefits than those in groups B and C (P<0.001). CONCLUSIONS: Improvement in serum 5-HT concentrations has obvious association with primary premature ejaculation symptom improvement with paroxetine use.

[Case-control study on locking titanium plate in treating comminuted proximal humeral fracture in elderly].

OBJECTIVE: To observe therapeutic effects of locking titanium plate for the treatment of comminuted proximal humeral fracture in elderly. METHODS: From June 2011 to May 2013, 72 elderly patients with comminuted proximal humeral- fractures were divided into locking titanium plate group and anatomical plate group, 36 cases in each group. In locking titanium plate group, there were 16 males and 20 females aged from 60 to 79 years old with an average of (69.55±5.62) years old; 10 cases were type Neer II, 18 were type Neer III and 8 cases were type Neer IV in accordance with Neer classification; treated with locking titanium plate. In anatomical plate group, there were 15 males and 21 females aged from 60 to 81 years old with an average of (69.76±5.70) years old; 9 cases were type Neer II, 20 were type Neer III and 7 cases were type Neer IV; and treated with anatomical plate. Clinical effects, preoperative and postoperative Neer scoring, operative time, bone healing time and incidence of complications between two groups were compared. RESULTS: All patients were followed up from 1 to 3 years with an average of 15 months. The excellent and good rate of locking titanium plate group (91.7%) was significantly higher than anatomical plate group (75.0%). Postoperative Neer score of two groups were improved obviously, but locking titanium plate group (92.51±7.85) was higher than anatomical plate group (83.64±8.56); there was no significant differences between two groups in operative time (P>0.05); bone healing time in locking titanium plate was (18.6±3.4) weeks, and shorter than anatomical plate group (24.3±3.9) weeks; incidence of complications in locking titanium plate was (5.6%) shorter than anatomical plate group (22.2%), and had obviously differences between two groups. CONCLUSION: Locking titanium plate for the treatment of comminuted proximal humeral fracture in elderly plays an important role in good rate, bone healing time and Neer score. It has advantages of early rehabilitation exercise, less shoulder pain, rapid recovery of shoulder joint, less complications, safe and effective, and be worthy of clinical application, especially for senile osteoporosis patients.

[Progress in researches on stem cell therapy for erectile dysfunction].

Erectile dysfunction (ED) commonly results from endothelial dysfunction and erectile nerve damage. Recent researches have focused on the preclinical studies of stem cell-based therapies targeted at repairing penile endothelium and protecting erectile nerves. Early studies showed that stem cell- or gene-modified stem cell-based therapies may have enduring efficacy and eventually lead to a cure for ED. Such stem cells as embryonic, mesenchymal, muscle-derived and adipose-derived ones and endothelial progenitor cells all have differentiation potentials and obvious advantages in protecting and repairing both nervi erigentes and corpus cavernosum vascular endothelial cells. Stem cell-based therapies promise to be an effective approach to human erectile dysfunction.