An Effective Technique for Managing the Calcaneus Osteomyelitis Combined with Soft-Tissue Defect.

The treatment of the Cierny-Mader (C-M) type III-IV calcaneus osteomyelitis combining with the soft-tissue defect is sophisticated and difficult. The aim of this study is to introduce the application and availability of the modified distally based sural flap with an adipofascial extension to reconstruct these defects. We retrospectively reviewed the data of 37 patients with C-M type III-IV calcaneus osteomyelitis accompanied with soft-tissue defect between December 2004 and December 2019. A modified distally based sural flap with an adipofascial extension was conducted to reconstruct the defect. The patient's demographics, duration of the diseases, etiology, reconstruction outcomes, infection control rate, recurrence rate, amputation rate, and follow-up data were collected to evaluate the effectiveness and reliability of the modification. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot scale was applied to assess the function of the ankle and hindfoot. Thirty-four flaps survived uneventfully, 1 flap displayed marginal necrosis and 2 flaps (5.41%) developed partial necrosis. Using this modified flap alone or combining with some simple salvage methods reconstructed all of the defects successfully. The calcaneus osteomyelitis was cured successfully, and no recurrences were observed during the follow-up period. The AOFAS ankle and hindfoot scores were excellent in 27 patients and good in 8 patients. The distally based sural flap with an adipofacial extension is a simple and effective technique to reconstruct the calcaneus osteomyelitis combined with soft-tissue defect in 1 stage. Applications of the adipofacial extension to obliterate the dead space and the well-vascularized skin island to cover the defect are the guarantee of achieving good ankle and foot functions. However, this technique is not appropriate for the patients with calcaneum less than half weight-bearing area.

Missed Monteggia fractures in children treated by open reduction of the radial head and corrective osteotomy of the ulna.

Missed Monteggia fractures in children may cause pain, deformity, decreased range of motion, neurological symptoms, and late arthritis of the elbow. Numerous surgical techniques have been advocated to reconstruct missed Monteggia lesions. The purpose of the present study were first to evaluate the clinical and radiographic outcomes after open reduction of the radial head and corrective osteotomy of the ulna, second to identify the factors associated with the preoperative radial notch/head appearance and the postoperative radiographic results. This study investigated the preoperative MRI presentation and the treatment of 29 patients who were diagnosed missed Monteggia fracture. Radiologic and clinical results of these patients were evaluated retrospectively, and the patient's and surgical factors related to preoperative radial notch/head appearance and the postoperative radiographic results were analyzed. Of the 29 patients, the average Kim elbow performance score at the last follow-up was 93.6, with 25 excellent, three good, one fair, and no poor results. 19 children had reduced radial heads, 8 had a subluxated radial head and 2 had dislocated radial heads at the last follow-up. The patient's gender and age had no significant influence on the appearance of radial notch/head and final radiographic results. However, the appearance of radial notch/head can significantly affect the final radiographic result (P < 0.001). The interval time was an important factor which related with the appearance of radial notch/head and final radiographic results (P < 0.001). Treating a missed Monteggia fracture by open reduction of the radial head and corrective osteotomy of the ulna is generally successful and preoperative MRI is meaningful for evaluation of the condition of the radial head and the radial notch which is related with the final radiographic result. The interval time from injury to operation exceeds 6 months, the risk of radial notch/head abnormality and radial head subluxation/re-dislocation after operation significantly increase.

[Sex differences in clinical outcomes of extremely preterm infants/extremely low birth weight infants: a propensity score matching study]. / è¶ æ—©äº§å„¿/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ä¸´åºŠç»“å±€çš„æ€§åˆ«å·®å¼‚ï¼šä¸€é¡¹å€¾å‘æ€§è¯„åˆ†åŒ¹é ç ”ç©¶.

OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Distally Based Perforator-Plus Sural Neurocutaneous Flap with High or Low Pivot Point: Anatomical Considerations and a Retrospective Study of a Clinical Series of 378 Flaps.

BACKGROUND: This study is to describe the distribution of natural true anastomoses associated with the distally based perforator-plus sural neurocutaneous flap (sural flap), summarize our experience in the flap with high pivot point, and compare the outcomes between the flaps with high and low pivot points. METHODS: Five amputated lower limbs were perfused, and the integuments were radiographed. We retrospectively analyzed 378 flaps, which were divided into two groups: pivot points located ≤8.0 cm (low pivot point group) and >8.0 cm (high pivot point group) proximal to the tip of the lateral malleolus. Partial necrosis rates were compared between two groups. RESULTS: The arterial chain surrounding the sural nerve was linked by true anastomoses from the intermalleolar line to popliteal crease. True anastomoses existed among peroneal perforators and between these perforators and the arterial chain. There were 93 flaps with high pivot point and 285 flaps with low pivot point. Partial necrosis rates were 16 and 9.1% in the high and low pivot point group (p = 0.059), respectively. CONCLUSION: True anastomosis connections among peroneal perforators and the whole arterial chain around sural nerve enable the sural flap to survive with a greater length. The sural flap with high pivot point is a good option for reconstructing soft-tissue defects in the middle and distal leg, ankle, and foot, particularly when the lowest peroneal perforator presents damage, greater distance to the defects, discontinuity with the donor site, or anatomical variation.

Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells.

PURPOSE: This study aimed to investigate the potential mechanism and value of lupeol in inhibiting high-glucose-induced apoptosis in rabbit nucleus pulposus cells (NPCs). METHODS: NPCs were divided into four groups: control (CON), high glucose (HG), LUP, and HG + LUP. Viability, reactive oxygen species (ROS) levels, and apoptosis were examined in NPCs. The protein expression levels of Bax, Bcl-2, cytochrome C, and caspase 9/3 were measured using reverse transcription-polymerase chain reaction and Western blot assay. RESULTS: The apoptotic rate and total ROS level of the HG group significantly increased compared with the CON group (P < 0.01). The total ROS level in the HG + LUP group significantly decreased compared with the HG group(P < 0.05). The mRNA expression of Bcl-2 was significantly upregulated, whereas the expression of Bax, cytochrome C, and caspase 9/3 was downregulated in the HG + LUP group compared with those in the HG group(P < 0.05).The Western blot assay showed that the expression of Bcl-2 was upregulated, but the expression of Bax, cytochrome C, and caspase 9/3 was significantly downregulated in the HG + LUP group compared with the HG group (P < 0.05). CONCLUSIONS: Lupeol inhibited high-glucose-induced apoptosis in NPCs by enhancing the anti-oxidative stress in the mitochondria. This study suggested lupeol as a potential therapeutic drug for treating intervertebral disc degeneration under hyperglycaemic conditions. These slides can be retrieved under Electronic Supplementary Material.

EGFR/EGFRvIII remodels the cytoskeleton via epigenetic silencing of AJAP1 in glioma cells.

EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing. Therefore, we deduced that in glioma cells, the pathway downstream of EGFR remodels the cytoskeleton via AJAP1 epigenetic silencing to enhance invasion. Furthermore, MK2206 reversed AJAP1 downregulation by inhibiting the EGFR pathway. In vivo, MK2206 also inhibited the proliferation and local invasion of 87-EGFRvIII. These data suggest that activation of the EGFR signal transduction pathway genetically silences anti-oncogenes to enhance GBM malignancy. MK2206 might be a promising therapeutic for EGFR/EGFRvIII-positive GBMs.

Signal Peptide Peptidase, Encoded by HM13, Contributes to Tumor Progression by Affecting EGFRvIII Secretion Profiles in Glioblastoma.

BACKGROUND AND AIMS: EGFRvIII is the most prevalent glioblastoma mutation, occurring in more than 25% of glioblastomas. EGFRvIII cells release microvesicles that contain proteins, miRNAs, and mRNAs that enhance the growth and survival of surrounding tumor cells. However, little is known about the maturation process and regulatory mechanisms of secreted vesicles in EGFRvIII cells. METHODS: Signal peptide peptidase (SPP) provides a fascinating mechanism for protein cleavage and subsequent dislocation in the endoplasmic reticulum transmembrane domain. RESULTS: In this study, we reported that SPP facilitates the secretion of cytokines in vitro and promotes tumor progression in mice. Human cytokine antibody arrays revealed that EGFRvIII secreted higher levels of cytokines, but these levels were significantly reduced following SPP knockdown, suggesting that cytokines in EGFRvIII secretion profiles play important roles in GBM development. Identical results were confirmed in intracellular maturation tracking of TGF-ß1 in mouse serum. Clinically, analyses of GBM patient data from the database revealed that HM13 expression was closely related to patient prognosis and survival, suggesting an influence by the secreted vesicles of EGFRvIII tumor cells. CONCLUSIONS: Collectively, our study identifies that SPP affects EGFRvIII secretion profiles and thus promotes tumor progression, providing further understanding of the formation of secreted vesicles and driving role of EGFRvIII in GBM.

The CRISPR/Cas9 system targeting EGFR exon 17 abrogates NF-κB activation via epigenetic modulation of UBXN1 in EGFRwt/vIII glioma cells.

Worldwide, glioblastoma (GBM) is the most lethal and frequent intracranial tumor. Despite decades of study, the overall survival of GBM patients remains unchanged. epidermal growth factor receptor (EGFR) amplification and gene mutation are thought to be negatively correlated with prognosis. In this study, we used proteomics to determine that UBXN1 is a negative downstream regulator of the EGFR mutation vIII (EGFRvIII). Via bioinformatics analysis, we found that UBXN1 is a factor that can improve glioma patients' overall survival time. We also determined that the down-regulation of UBXN1 is mediated by the upregulation of H3K27me3 in the presence of EGFRvIII. Because NF-κB can be negatively regulated by UBXN1, we believe that EGFRwt/vIII activates NF-κB by suppressing UBXN1 expression. Importantly, we used the latest genomic editing tool, CRISPR/Cas9, to knockout EGFRwt/vIII on exon 17 and further proved that UBXN1 is negatively regulated by EGFRwt/vIII. Furthermore, knockout of EGFR/EGFRvIII could benefit GBM in vitro and in vivo, indicating that CRISPR/Cas9 is a promising therapeutic strategy for both EGFR amplification and EGFR mutation-bearing patients.

Non-coding RNAs as regulators in epigenetics (Review).

Epigenetics is a discipline that studies heritable changes in gene expression that do not involve altering the DNA sequence. Over the past decade, researchers have shown that epigenetic regulation plays a momentous role in cell growth, differentiation, autoimmune diseases, and cancer. The main epigenetic mechanisms include the well-understood phenomenon of DNA methylation, histone modifications, and regulation by non-coding RNAs, a mode of regulation that has only been identified relatively recently and is an area of intensive ongoing investigation. It is generally known that the majority of human transcripts are not translated but a large number of them nonetheless serve vital functions. Non-coding RNAs are a cluster of RNAs that do not encode functional proteins and were originally considered to merely regulate gene expression at the post-transcriptional level. However, taken together, a wide variety of recent studies have suggested that miRNAs, piRNAs, endogenous siRNAs, and long non-coding RNAs are the most common regulatory RNAs, and, significantly, there is a growing body of evidence that regulatory non-coding RNAs play an important role in epigenetic control. Therefore, these non-coding RNAs (ncRNAs) highlight the prominent role of RNA in the regulation of gene expression. Herein, we summarize recent research developments with the purpose of coming to a better understanding of non-coding RNAs and their mechanisms of action in cells, thus gaining a preliminary understanding that non-coding RNAs feed back into an epigenetic regulatory network.

F25P preproinsulin abrogates the secretion of pro-growth factors from EGFRvIII cells and suppresses tumor growth in an EGFRvIII/wt heterogenic model.

Extensive heterogeneity is a defining hallmark of glioblastoma multiforme (GBM) at the cellular and molecular levels. EGFRvIII, the most common EGFR mutant, is expressed in 24-67% of cases and strongly indicates a poor survival prognosis. By co-expressing EGFRvIII and EGFRwt, we established an EGFRvIII/wt heterogenic model. Using this approach, we confirmed that a mixture of EGFRvIII and EGFRwt at a certain ratio could clearly enhance tumor growth in vitro and in vivo compared with EGFRwt cells, thereby indicating that EGFRvIII cells promote tumor growth. Furthermore, we demonstrated that the EGFRvIII cells could support the growth of EGFRwt cells by secreting growth factors, thus acting as the principal source for maintaining tumor survival. F25P preproinsulin effectively reduced the concentrations of EGF, VEGF, and MMP-9 in the blood of tumor-bearing mice by competitively inhibiting the endoplasmic reticulum signal peptidase and increased the overall survival in orthotopic models. Taken together, our results provided an effective therapy of F25P preproinsulin in the EGFRvIII/wt heterogenic model.

A Modified Technique to Improve Reliability of Distally Based Sural Fasciocutaneous Flap for Reconstruction of Soft Tissue Defects Longitudinal in Distal Pretibial Region or Transverse in Heel and Ankle.

Partial flap loss is a common complication of the distally based sural fasciocutaneous flap. We present a modified technique of a sloped skin island design to improve the reliability of the flap when used to reconstruct a longitudinal distal pretibial defect or transverse heel and ankle defect. Thirty-one flaps with the slope-designed skin island were used to reconstruct such defects in 30 patients. In the modified technique, the skin island was rotated toward the vascular axis of the flap. The defects were located in the distal pretibial region in 7 cases and the ankle and heel region in 24. The horizontal dimension of the skin island decreased by an average of 5.6 (range 2.5 to 14.8) cm with the sloped design, and the rotation angle varied from 42° to 90° (mean 69°). Of the 31 flaps, 29 survived, 1 developed marginal necrosis, and 1 developed lateral partial necrosis. The sloped design of the skin island is applicable to reconstruction of longitudinal distal pretibial or transverse heel and ankle defects. The modified technique can decrease the horizontal dimension and increase perfusion of the skin island, thus improving the reliability of the flap.

Distally based perforator-plus sural fasciocutaneous flap for soft-tissue reconstruction of the distal lower leg, ankle, and foot: comparison between pediatric and adult patients.

There are no large series comparing the distally based perforator-plus sural fasciocutaneous flap used in pediatric and adult populations. The flaps were divided into two groups: the children (patient's age<14 years) group (n=53) and the adults (patient's age ≥ 18 years) group (n=148). We compared flap-viability-related complications and their potential risk factors. In the patients with at least 12-month postoperative follow-up, the reconstruction outcomes, donor-site morbidities, and transitory and permanent swelling of the affected lower limb were compared. Partial necrosis, marginal necrosis, and overall complication rates were 13.2, 3.8, and 17.0% in the pediatric group, and 12.2, 1.4, and 13.6% in the adult group, respectively; the differences were not statistically significant (p>0.05). Incidences of hypertrophic scar and pruritus at the donor site were significantly higher, while incidence of transitory swelling of the affected lower limb was significantly lower in the pediatric group. This flap in children is similar to that in adults in the reliability.

Anterograde-retrograde method for harvest of distally based sural fasciocutaneous flap: report of results from 154 patients.

Distally based sural fasciocutaneous flap is traditionally raised by the retrograde method. This article introduces the anterograde-retrograde method for harvest of the flap and describes our experience on altering the flap plan. A total of 159 flaps in 154 patients were elevated by the anterograde-retrograde approach that harvest of the flap began with exploring the peroneal artery perforators nearby the pivot point before the upper and bilateral edges of the flap were incised. Partial necrosis occurred in 16 (10.1%) flaps, and marginal necrosis developed in 10 flaps. Nine flaps were redesigned with adjusted pivot point and skin island. The anterograde-retrograde approach for harvest of the flap can accurately locate the perforator, readily adjust both the pivot point and skin island if necessary, and thus improve reliability of the flap. This approach is particularly applicable for elevation of the flap without preoperative localization of the perforators by means of the Doppler.

Influence of flap factors on partial necrosis of reverse sural artery flap: a study of 179 consecutive flaps.

BACKGROUND: Partial necrosis is a main complication of reverse sural artery flap. The purpose of this article is to evaluate effect of flap factors on partial necrosis in the flap. PATIENTS AND METHODS: We retrospectively reviewed data of 175 patients with 179 flaps used to reconstruct soft tissue defects in the distal lower leg, heel, and foot between April 2001 and April 2010. Posterior aspect of the lower leg was equally divided into nine zones. The flap factors were compared between the survival flaps and the partial-necrosis flaps. RESULTS: There were 141 flaps surviving completely; distal de-epithelialization and wound dehiscence developed in 12 flaps and 6 flaps, respectively; partial necrosis occurred in 20 (11.2%) flaps. Partial-necrosis rate was significantly higher in the flaps with top-edge locating in the upper 1/9 of the calf (32.3%, 10 of 31), in the flaps with length-width ratio (LWR) ≥5:1 (17.8%, 13 of 73), or in the flaps with width of skin island (width) ≥8 cm (15.2%, 16 of 105); it was significantly lower in the flaps with top-edge locating in the lower 7/9 of the calf (3.8%, 3 of 80). Seventeen (80.9%) of 21 flaps with LWR ≥6:1 survived, and the maximal LWR of completely survival flap was 7.00:1. CONCLUSION: Probability of partial necrosis occurring in reverse sural artery flap significantly increase when top-edge of the flap locates in the upper 1/9 of the calf, when LWR of the flap is 5:1 or more, or when width is 8 cm or more. The flap with top-edge locating lower 7/9 of the calf is safe and reliable.

The upper thoracic spinal cord compression as the initial manifestation of Wegener's granulomatosis: a case report.

There are only a few reported cases about spinal cord involvement with Wegener's granulomatosis (WG) in the literature. In these cases, the spinal cord is usually indented or compressed by dural and meningeal masses which are characterized by necrotizing granuloma formation and vasculitis. And, it usually cannot be correctly diagnosed. A 53-year-old woman suffered from Wegener's granulomatosis, in whom the upper thoracic spinal cord compression is the initial manifestation. The surgical biopsy and thoracic laminectomy were performed and the histologic examination was done. This patient was finally diagnosed as WG when the pathologic examination revealed as Wegener's granulomatosis and the serum antineutrophil cytoplasmic antibodies (ANCA) were reported positive; titers of antimyeloperoxidase (MPO) antibodies were markedly elevated. After treatment with cyclophosphamide and corticosteroids this patient partially recovered from neurological involvement. In a case such as this, careful monitoring of clinical parameters is essential for assessing disease activity with repeated MRI if neurologic status changes. Serial measurement of ANCA titers may also be helpful to establish the diagnosis. Cyclophosphamide and corticosteroids are the agents of choice for induction of remission of WG.