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ICLR submission. This work is supported in part by the Huawei Technologies Co., Ltd under Grant HIRP2019041002010, the Horizon Europe: European Lighthouse on Secure and Safe AI – ELSA, the UK EPSRC under Grant EP/P009727/1, and the Leverhulme Trust under Grant RF-2019-492

Diabetes mellitus (DM) impairs the wound healing process, seriously threatening the health of the diabetic population. To date, few effective approaches have been developed for the treatment of diabetic wounds. Krill oil (KO) contains bioactive components that have potent anti-inflammatory and anti-oxidative activities. As prolonged inflammation is a crucial contributor to DM-impaired wound healing, we speculated that the local application of KO would accelerate diabetic wound healing. Therefore, KO was applied to artificially created wounds of type 2 diabetic mice induced by streptozotocin and high-fat diet. The diabetic mice had a delayed wound healing process compared with the non-diabetic control mice, with excessive inflammation, impaired collagen deposition, and depressed neovascularization in the wound area. These effects were dramatically reversed by KO. In vitro, KO blocked the TNF-α-induced macrophage inflammation, fibroblast dysfunction, and endothelial angiogenic impairment. The present study in mice suggests that KO local application could be a viable approach in the management of diabetic wounds.

Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the posterior tibial nerve or its terminal branches compressed by its fibro-osseous tunnel beneath the flexor retinaculum on the medial side of the ankle. The current study was a retrospective study of 107 cases of patients with TTS, in which the onset characteristics were summarized, the factors that might affect the surgical treatment effects of TTS were discussed and analyzed. The syndrome diagnoses and treatment experiences of TTS were extracted and analyzed. In our cohort, TTS was more often found in middle-aged and older women. And the medial plantar nerve bundle was the most frequently affected nerve structure. The efficacy of surgical treatment were correlated to the causes of the disease, involved nerve bundles, methods of operation, and whether neurolysis of the epineurium was performed. Neurolysis of the epineurium is was recommended for patients with an enlarged tibial nerve due to impingement. The Singh method was recommended to release the tibial nerve and its branches. Patients with negative preoperative EMG results should carefully be cautious when considering their decision to undergo surgical treatment.

Over a half of the diabetic individuals develop macrovascular complications that cause high mortality. Oxidative stress (OS) promotes endothelial dysfunction (ED) which is a critical early step toward diabetic macrovascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system and combats diabetes-induced OS. Previously, we found that impaired NRF2 antioxidant signaling contributed to diabetes-induced endothelial OS and dysfunction in mice. The present study has investigated the effect of microRNA-200a (miR-200a) on NRF2 signaling and diabetic ED. In aortic endothelial cells (ECs) isolated from C57BL/6 wild-type (WT) mice, high glucose (HG) reduced miR-200a levels and increased the expression of kelch-like ECH-associated protein 1 (Keap1) – a target of miR-200a and a negative regulator of NRF2. This led to the inactivation of NRF2 signaling and exacerbation of OS and inflammation. miR-200a mimic (miR-200a-M) or inhibitor modulated KEAP1/NRF2 antioxidant signaling and manipulated OS and inflammation under HG conditions. These effects were completely abolished by knockdown of Keap1, indicating that Keap1 mRNA is a major target of miR-200a. Moreover, the protective effect of miR-200a-M was completely abrogated in aortic ECs isolated from C57BL/6 Nrf2 knockout (KO) mice, demonstrating that NRF2 is required for miR-200a’s actions. In vivo, miR-200a-M inhibited aortic Keap1 expression, activated NRF2 signaling, and attenuated hyperglycemia-induced OS, inflammation and ED in the WT, but not Nrf2 KO, mice. Therefore, the present study has uncovered miR-200a/KEAP1/NRF2 signaling that controls aortic endothelial antioxidant capacity, which protects against diabetic ED.

Objective Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells. Materials and Methods Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo. Results qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo. Conclusion This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.

Flavonoids are present in a wide range of plants. They have been used in the treatment of cancer, but the mechanism underlying this activity is unclear. In recent years, microRNA (miRNA) and long non-coding RNA (lncRNA) levels have been observed to differ between normal tissues and cancer cells, and both types of RNA have been shown to have a role in tumor treatment. In addition, flavonoids have been proven to regulate miRNAs and LncRNAs in the treatment of cancer. The competing endogenous RNA (ceRNA) network is a complex post-transcriptional regulatory mechanism in cells, in which coding and non-coding RNAs competitively bind miRNAs to regulate messenger RNAs (mRNAs). This review focused on the role of the ceRNA network in the treatment of cancer by flavonoids.

BackgroundChrysin is a natural flavone that is present in honey and has exhibited anti-tumor properties. It has been widely studied as a therapeutic agent for the treatment of various types of cancers. The objectives of this present study were to elucidate how chrysin regulates non-coding RNA expression to exert anti-tumor effects in gastric cancer cells.MethodsThrough the use of RNA sequencing, we investigated the differential expression of mRNAs in gastric cancer cells treated with chrysin. Furthermore, COPB2, H19 and let-7a overexpression and knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion, were also analyzed. Knockout of the COPB2 gene was generated using the CRISPR/Cas9 system for tumor growth analysis in vivo.ResultsOur results identified COPB2 as a differentially expressed mRNA that is down-regulated following treatment with chrysin. Moreover, the results showed that chrysin can induce cellular apoptosis and inhibit cell migration and invasion. To further determine the underlying mechanism of COPB2 expression, we investigated the expression of the long non-coding RNA (lncRNA) H19 and microRNA let-7a. Our results showed that treatment with chrysin significantly increased let-7a expression and reduced the expression of H19 and COPB2. In addition, our results demonstrated that reduced expression of COPB2 markedly promotes cell apoptosis. Finally, in vivo data suggested that COPB2 expression is related to tumor growth.ConclusionsThis study suggests that chrysin exhibited anti-tumor effects through a H19/let-7a/COPB2 axis.

Liver fibrosis is a serious health problem and may lead to advanced liver cirrhosis and hepatocellular carcinoma if left untreated. In this study, a mouse liver fibrosis model was established by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and tanshinone IIA. Salvia miltiorrhiza Bunge extract, shown to play a regulatory role in liver fibrosis, was administered to study its effect on the expression of COL1A1. Mice were divided into 3 groups, control (Con), model (DDC), and drug administration (DDC-Tan) groups, and were subjected to the respective treatment for 2 months. Following treatment, the degree of liver fibrosis in mice in each group was determined. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and albumin levels in mice were determined using enzyme-linked immunosorbent assay (ELISA). Mouse liver tissues were used for hematoxylin-eosin and immunohistochemical staining. ELISA results showed that treatment with tanshinone IIA inhibited the expression of ALT, AST, and bilirubin in the DDC-Tan group compared with the DDC group. Hematoxylin-eosin, Sirius red, and α-SMA staining showed that liver injury was delayed in the DDC-Tan group. Immunohistochemistry, quantitative polymerase chain reaction, and Western blot results showed that COL1A1 expression was reduced after tanshinone IIA treatment. Moreover, the bioinformatic analysis indicated that let-7a targets COL1A1, and H19 regulates let-7a expression. The quantitative polymerase chain reaction and Western blot results confirmed that the H19/let-7a axis regulates COL1A1 expression. Thus, tanshinone IIA inhibited liver fibrosis by regulating COL1A1 expression through the H19/let-7a axis in mice.

Metacarpals are unique bones that support the finger to aid hand function. Metacarpals are also the commonest bones to get fractured in the hand. Historically, most metacarpal fractures were managed conservatively. Due to increased patient expectations as well as advancements in diagnosis and osteosynthesis, various surgical options are now available for metacarpal fractures. The goal of operative management of metacarpal management is no longer limited to achieving clinical or radiological union. To restore hand function to a preinjury level, the surgeon must achieve adequate anatomical reduction and stable fixation with minimal soft tissue damage. Similar to tendon repair, to start early active motion should be the goal after metacarpal fracture fixation. Intraoperative consideration should also include minimizing soft tissue damage and avoiding tendon, ligament or capsular entrapment. The aim of this article is to explain the principles of surgical management, the different options available for metacarpal fractures, the techniques, pearls, advantages and disadvantages of each technique, so the surgeon can choose the ideal option to achieve the best result.

Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)‐treated endothelial cells (ECs) were subjected to pifithrin‐α (PFT‐α)—a specific inhibitor of P53, or P53‐small interfering RNA (siRNA), both of which attenuated the HG‐induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT‐α or P53‐siRNA prohibited P53 acetylation, decreased microRNA‐34a (miR‐34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR‐34a inhibitor (miR‐34a‐I) and PFT‐α increased SIRT1 protein level and alleviated the HG‐induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT‐α were completely abrogated by the miR‐34a mimic. In addition, SIRT1 inhibition by EX‐527 or Sirt1‐siRNA completely abolished miR‐34a‐I's protection against HG‐induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin‐induced diabetic mice, both PFT‐α and miR‐34a‐I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycaemia. Hence, the present study has uncovered a P53/miR‐34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR‐34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases.

Methylation of the adenine base at the nitrogen 6 position (m6A) is the most common post-transcriptional epigenetic modification of RNA, and it plays a very important role in regulating gene expression. To investigate the role of m6A methylation in the expression of non-coding RNA and miRNA, we used a system of adenine base editors (ABEs). Here, we mutated regions up- and downstream of miRNA 675 m6A modification sites in the H19 locus using HEK293T, L02, MHCC97L, MHCC97H, A549, and SGC-7901 cells. Our results showed that a T–A base transversion had occurred in all cell lines. Moreover, mutation of the regions upstream of the miRNA 675 m6A modification site led to reduced expression of H19 and the induction of cell apoptosis in HEK293T cells. To further confirm our results, L02 and MHCC97L cells were detected using ABEs system. The results indicated increased cell apoptosis and reduced expression of miR675 as well as H19. To confirm the relationship between H19 and miR675 expression, overexpression and knockdown studies were performed. The results showed that reduced HI9 expression induced cell apoptosis through miR675. Taken together, these results indicate that m6A modification can regulate the expression of H19 and miR675 which induce cell apoptosis.

The application of surface enhanced infrared absorption (SEIRA) is severely restricted in many fields due to the SEIRA substrates are constructed mainly from expensive noble metals. Therefore, the development of new SEIRA substrates other than the noble metallic ones is very valuable. Here we introduced a new semiconductor SEIRA substrate, the indium tin oxide (ITO) nanoparticles (NPs), to study the SEIRA property. The results demonstrate that the ITO NPs show the SEIRA property and the enhancement is dependent to the doping ratio of the heteroatoms of tin. The ITO NPs with the 5% atomic doping ratio show the highest SEIRA enhancement factor (EF), which is about 24. The limit of detection (LOD) of the 1,1'-dicarboxyferrocene (dcFc) molecule was as low as 10

Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) – a master of cellular antioxidants scavenging excessive DM-induced free radicals – in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation and accelerated wound closure in diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG) or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) – inducible in DM – in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing.

Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells.Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo.qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo.This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.

BACKGROUND Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. METHODS For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. RESULTS Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. CONCLUSION Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction.

Aberrant epigenetic modification, including N6-methylation of adenosine (m6A), has been frequently reported in embryos derived from parthenogenetic activation (PA). However, the role of Igf2bp1 expression pattern in m6A modification and the mechanism through which Igf2bp1 function is regulated in PA embryos remains elusive. Therefore, in this study, using si-Igf2bp1 and betaine (N,N,N-trimethylglycine, a major methyl donor), we investigated the effect of Igf2bp1 expression in m6A modification on the development of PA embryos. The results indicated that the down-regulation of Igf2bp1 reduced the cleavage and blastula rates of PA embryos. Moreover, m6A expression level was markedly down-regulated following microinjection with si-Igf2bp1. However, the treatment with betaine could significantly restore the m6A level. Further bioinformatics analysis revealed Igf2bp1 as the putative target of microRNA 670 (miR-670). Thus, to confirm this finding, mimics and inhibitor of miR-670 were microinjected into PA embryos. The results demonstrated that miR-670 inhibitor augmented the expression of Igf2bp1 and rescued cleavage and blastula rates. In addition, the miR-670 inhibitor promoted the m6A expression level. TUNEL assay revealed a loss of expression of Igf2bp1 induced cell apoptosis in PA embryos. Taken together, these results demonstrated that miR-670-3p functions as the regulator of Igf2bp1 expression and plays a crucial role in PA development through m6A modification.

Macrovascular complications develop in over a half of the diabetic individuals, resulting in high morbidity and mortality. This poses a severe threat to public health and a heavy burden to social economy. It is therefore important to develop effective approaches to prevent or slow down the pathogenesis and progression of macrovascular complications of diabetes (MCD). Oxidative stress is a major contributor to MCD. Nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) governs cellular antioxidant defence system by activating the transcription of various antioxidant genes, combating diabetes‐induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch‐like ECH‐associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of the Nfe2l2 gene transcription, decreasing KEAP1 protein level by microRNA‐induced degradation of Keap1 mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in prevention of MCD. This review provides a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review.

Behavioural phenotyping of drosphila is an important means in biological and medical research to identify genetic, pathologic or psychologic impact on animal behviour. Automated behavioural phenotyping from videos has been a desired capability that can waive long-time boring manual work in behavioral analysis. In this paper, we introduced deep learning into this challenging topic, and proposed a new 2D+3D hybrid CNN framework for drosphila’s social behavioural phenotyping. In the proposed multitask learning framework, action detection and localization of drosphila jointly is carried out with action classification, and a given video is divided into clips with fixed length. Each clip is fed into the system and a 2-D CNN is applied to extract features at frame level. Features extracted from adjacent frames are then connected and fed into a 3-D CNN with a spatial region proposal layer for classification. In such a 2D+3D hybrid framework, drosophila detection at the frame level enables the action analysis at different durations instead of a fixed period. We tested our framework with different base layers and classification architectures and validated the proposed 3D CNN based social behavioral phenotyping framework under various models, detectors and classifiers.

This study aimed to compare the long-term efficacy of Kirschner wires and Herbert screw internal fixation in scaphoid fracture. A retrospective chart with radiographic review and functional follow-up was conducted for patients with the scaphoid fracture. 65 patients (40 for K-wire fixation and 25 for Herbert screw) were enrolled. The nonunion rate for K-wire fixation and screw method were indifferent comprehensively and for iliac graft subgroup. Less bone necrosis was found with K-wire fixation (2.5% vs 16%, P=0.049). There's no difference between groups in Mayo scores, post-operation pain and grid strength. Patients with K-wire fixation have larger range of motion on radial/ulnar deviation (35.25±11.32 vs 28.00±8.66, P=0.007). The results support the use of Kirschner wires in the treatment of scaphoid fractures. Advantages such as high union rates and good function recovery of wrist could be expected from minimal invasion, multi-axial stable fixation.

Diabetic nephropathy (DN) is the leading cause of end stage renal disease, posing a severe threat to public health. Previous studies reported the protective role of sirtuin 1 (SIRT1) in DN, encouraging the investigation of more potent and specific SIRT1 activators. SRT2104 is a novel, first-in-class, highly selective small-molecule activator of SIRT1, with its effect and mechanism unknown on DN. To this end, streptozotocin-induced C57BL/6 wild-type (WT) diabetic mice were treated with SRT2104, for 24 weeks. To determine whether SRT2104 acted through inhibition of P53 – a substrate of SIRT1, the P53 activator nutlin3a was administered to the WT diabetic mice in the presence of SRT2104. In order to test whether nuclear factor erythroid 2-related factor 2 (NRF2) – the master of cellular antioxidants – mediated SIRT1 and P53's actions, WT and Nrf2 gene knockout (KO) diabetic mice were treated with SRT2104 or the P53 inhibitor pifithrin-α (PFT-α). In the WT mice, SRT2104 enhanced renal SIRT1 expression and activity, deacetylated P53, and activated NRF2 antioxidant signaling, providing remarkable protection against the DM-induced renal oxidative stress, inflammation, fibrosis, glomerular remodeling and albuminuria. These effects were completely abolished in the presence of nutlin3a. Deletion of the Nrf2 gene completely abrogated the efficacies of SRT2104 and PFT-α in elevating antioxidants and ameliorating DN, despite their abilities to activate SIRT1 and inhibit P53 in the Nrf2 KO mice. The present study reports the beneficial effects of SRT2104 on DN, uncovering a SIRT1/P53/NRF2 pathway that modulates the pathogenesis of DN.

Testicular apoptotic cell death (TACD) contributes to diabetes mellitus (DM)-induced male infertility. MicroRNA-34a (miR-34a) is a pro-apoptotic RNA that targets sirtuin 1 (SIRT1) which provides protection against complications of (DM). However, the specific role of miR-34a in (DM)-induced TACD is unknown. MiR-34a targets Sirt1 mRNA, resulting in apoptosis. However, whether or not SIRT1 is a major target of miR-34a in (DM)-induced TACD is unclear. The present study aimed to define the role of miR-34a/SIRT1 in (DM)-induced TACD. C57BL/6 male mice were induced to (DM) by streptozotocin, for a period of 24 weeks. The expression of miR-34a and Sirt1 as well as apoptotic cell death was determined in the testes of the non-diabetic, diabetic, and the miR-34a-specific inhibitor (miR-34a-I)-treated diabetic mice. In addition, the novel SIRT1 activator SRT2104 was delivered to the mice to determine the role of SIRT1 in DM-induced TACD. The diabetic mice developed remarkable testicular oxidative stress, endoplasmic reticulum stress, and apoptotic cell death, the effects of which were significantly and similarly attenuated by both miR-34a-I and SRT2104. Mechanistically, the DM-induced testicular elevation of miR-34a and the decrease in SIRT1 protein were markedly prevented by both miR-34a-I and SRT2104, to a similar extent. The present study demonstrates a critical role of miR-34a/SIRT1 in DM-induced TACD, providing miR-34a inhibition and SIRT1 activation as novel strategies in clinical management of DM-induced male infertility.MiR-34a mediates diabetes-induced TACD via inhibition of SIRT1. The novel SIRT1 activator SRT2104 attenuates diabetes-induced TACD. MiR-34a inhibition activates SIRT1 and prevents diabetes-induced TACD.

Objective The posterior thigh region has been neglected as a donor site for free perforator flaps, likely due to difficulties in positioning the patient during surgery. This study describes the clinical application of the posterior thigh perforator flap based on the third perforating artery of the profunda femoris artery (PFA). Methods The free posterior thigh perforator flap based on the third perforating artery of the PFA was used for reconstruction of soft tissue defects in nine patients between February 2010 and May 2014. Results Flap sizes ranged from 12 × 7 cm to 20 × 13 cm. The length of the vascular pedicle averaged 10.28 cm, and the mean diameters of the third perforating artery and venae comitantes were 1.68 and 1.14 mm, respectively. All of the perforators originated from the PFA. Of the 9 free flaps used in 9 patients, 7 flaps survived completely. There were no early complications in these flaps. During the follow-up period, no patient experienced cold intolerance, scar contracture, or scar pain. There were no functional impairments at the donor or recipient sites. Conclusions The posterior thigh flap based on the third perforating artery of the PFA is an excellent option for reconstructing soft tissue defects. The anatomical location of the third perforating artery is relatively consistent. The vascular pedicle is relatively longer and has large caliber vessels. The scar at the donor site can be well concealed with low morbidity. The skin color and texture of this flap show satisfactory results.

Purpose The aim of this study was to analyze the differences in perioperative complications for pedicled island flaps in the reconstruction of extremities and to identify the factors contributing to pedicled island flap necrosis. Furthermore, the flap indications based on these outcomes are summarized. Methods Based on the inclusion criteria, 228 skin flaps were included in this study. Univariate and multivariate analyses were used to identify the risk factors for pedicled island flap necrosis. Differences in perioperative complications between upper and lower extremities were analyzed using the chi-square test or Fisher's exact test. Results The average age of the patients was 38 years. The overall complication rate was 21.93%, including partial flap necrosis (10.09%) and total flap necrosis (5.70%). The overall complication rate and flap necrosis rate in upper extremity reconstruction were significantly lower than the rates in lower extremity reconstruction. Flap area and postoperative wound infection were statistically significant risk factors for pedicled island flap necrosis in extremity reconstruction. Preoperative contamination of the wound bed was a statistically significant risk factor for postoperative wound infection. Conclusions The flap area and postoperative wound infection were both independent risk factors for pedicled island flap necrosis in extremity reconstruction. The causes contributing to the differences in perioperative complications between upper and lower extremities reconstruction included preoperative contamination of the wound bed, postoperative wound infection, and the flap area but were also related to anatomical factors of the skin flap. Pedicled island flaps are more suitable for small- and medium-sized soft tissue defects.