Mitochondrial homeostasis regulation: A promising therapeutic target for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) or Lewy neurites (LNs) which consist of α-synuclein (α-syn) and a complex mix of other biomolecules. Mitochondrial dysfunction is widely believed to play an essential role in the pathogenesis of PD and other related neurodegenerative diseases. But mitochondrial dysfunction is subject to complex genetic regulation. There is increasing evidence that PD-related genes directly or indirectly affect mitochondrial integrity. Therefore, targeted regulation of mitochondrial function has great clinical application prospects in the treatment of PD. However, lots of PD drugs targeting mitochondria have been developed but their clinical therapeutic effects are not ideal. This review aims to reveal the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases based on the mitochondrial structure and function, which may highlight potential interventions and therapeutic targets for the development of PD drugs to recover mitochondrial dysfunction in neurodegenerative diseases.

Polymerase iota (POLI) confers radioresistance of esophageal squamous cell carcinoma by regulating RAD51 stability and facilitating homologous recombination.

Radiotherapy resistance is an important and urgent challenge in the clinical management of esophageal squamous carcinoma (ESCC). However, the factors mediating the ESCC resistance to radiotherapy and its underlying molecular mechanisms are not fully clarified. Our previous studies have demonstrated the critical role of DNA polymerase iota (POLI) in ESCC development and progression, here, we aimed to investigate the involvement of POLI in ESCC radiotherapy resistance and elucidate the underlying molecular mechanism. We found that highly expressed POLI was correlated with shorter overall survival of ESCC patients received radiotherapy. Down-regulation of POLI sensitized ESCC to IR, prolonged γH2AX foci in nuclei and comet tails after IR. HR but not NHEJ repair is inhibited in POLI-deficient ESCC cells. POLI stabilizes RAD51 protein via competitively binding with and blocking the interaction between RAD51 and E3 ligase XIAP and XIAP-mediated ubiquitination. Furthermore, loss of POLI leads to the activation of GAS signaling. Our findings provide novel insight into the role of POLI in the development of radioresistance mediated by stabilizing RAD51 protein in ESCC.

Bone Grafting Can Promote the Prognosis of Displaced Femoral Neck Fractures: A Follow-up of the Clinical Significance of Bone Defects.

Background: Femoral neck fractures (FNFs) comprise a large proportion of osteoporotic fractures in Asia. However, the full range of prognostic variables that affect prognosis remains unclear. Here, we aimed to determine whether the severity of bone defects at the fracture site and other variables impact the prognosis of displaced FNFs. Methods: We evaluated the incidence of FNF internal fixation failures at regular intervals after surgery in data collected retrospectively. Digital Imaging and Communications in Medicine (DICOM) magnetic resonance imaging data of the displaced FNFs of 204 patients (> 20 years old; mean age, 52.3 years; men, 55.4%) who underwent internal fixation were used to construct three-dimensional (3D) virtual models of the femoral neck region. We calculated the position and volume of bone defect (VBD) using our independently developed algorithm and Mimics software. Each participant was followed up for at least 24 months; complications were noted and correlated with VBD and demographic and clinical variables. Results: On the basis of VBD values calculated from virtual reduction models, 57 patients were categorized as having a mild defect, 100 as having a moderate defect, and 47 as having a severe defect. Age (p = 0.046) and VBD (p < 0.001) were significantly correlated with internal fixation failure. Multivariate analysis revealed that severe bone defects were associated with internal fixation failure (adjusted odds ratio [aOR], 23.073; 95% confidence interval [CI], 2.791-190.732) and complications (aOR, 8.945; 95% CI, 1.829-43.749). In patients with a severe defect, bone grafting was inversely associated with internal fixation failure (aOR, 0.022; 95% CI, 0.002-0.268) and complications (aOR, 0.023; 95% CI, 0.002-0.299). Conclusions: Bone defect severity was associated with internal fixation failure and other complications. For young adults with large VBDs, bone grafting of the defect can reduce the risk of internal fixation failure. These results provide useful new quantitative information for precisely classifying displaced FNFs and guiding subsequent optimal treatments.

Can "In-Out-In" posterosuperior screws meet nutrient foramina in patients with femoral neck fractures?

BACKGROUND: The "In-Out-In" (IOI) posterosuperior screw was common in screw fixations of femoral neck fractures. The impacts of the IOI screw on the blood supply of the femoral head have not yet been clarified. The nutrient foramen was damaged when the screw was present in their corresponding cortex surface. This study aimed to evaluate the damage degrees of the nutrient foramina in the femoral neck as the IOI posterosuperior screw was placed in different posterosuperior locations. METHODS: One hundred and eight unpaired dry human cadaveric proximal femurs were scanned by a three-dimensional scanner. Digital data obtained from the proximal femur surface were employed for subsequent analysis. All nutrient foramina in the femoral neck were identified and marked in each subject. A simulation of the anteroposterior, lateral, and axial views was then performed, and regions of interest (ROIs) for IOI posterosuperior screws, with 6.5 mm diameter, were determined in the posterosuperior femoral neck on the axial graphs. Nutrient foramina were counted and analyzed in ROIs and femoral neck, and its damage from the IOI posterosuperior screw was also calculated in different conditions of screw placement. Paired t-tests were used for comparative analyses before and after damage. RESULTS: Most nutrient foramina were located in the subcapital region and the least in the basicervical region in the femoral neck, while the most were located in the transcervical and the least in the subcapital in the ROIs. In addition, most nutrient foramina in ROIs were located in the superior-posterior area of the femoral neck. There were four main locations of IOI posterosuperior screws where the decrease in the nutrient foramina was statistically significant (P < 0.01). The risk zone determined by these locations was located in a posterosuperior square of ROIs with an edge length of 9.75 mm. CONCLUSION: To minimize iatrogenic damage to the blood supply of the femoral head, screw positions could be assessed in anteroposterior and lateral radiographs using a risk zone. The IOI posterosuperior screw in ROIs can be applied to fix femoral neck fractures when feasible in clinical practice. This study could provide surgeons with more alternatives for screw placement in the posterosuperior femoral neck.

Clinical Evaluation of Femoral Head Fractures: Which Classification Systems Have the Best Universality, Reliability, and Reproducibility?

BACKGROUND: Femoral head fractures are rare but potentially disabling injuries, and classifying them accurately and consistently can help surgeons make good choices about their treatment. However, there is no consensus as to which classification of these fractures is the most advantageous; parameters that might inform this choice include universality (the proportion of fractures that can be classified), as well as, of course, interobserver and intraobserver reproducibility. QUESTIONS/PURPOSES: (1) Which classification achieves the best universality (defined as the proportion of fractures that can be classified)? (2) Which classification delivers the highest intraobserver and interobserver reproducibility in the clinical CT assessment of femoral head fractures? (3) Based on the answers to those two questions, which classifications are the most applicable for clinical practice and research? METHODS: Between January 2011 and January 2023, 254 patients with femoral head fractures who had CT scans (CT is routine at our institution for patients who have experienced severe hip trauma) were potentially eligible for inclusion in this study, which was performed at a large Level I trauma center in China. Of those, 9% (23 patients) were excluded because of poor-quality CT images, unclosed physes, pathologic fractures, or acetabular dysplasia, leaving 91% (231 patients with 231 hips) for analysis here. Among those, 19% (45) were female. At the time of injury, the mean age was 40 ± 17 years. All fractures were independently classified by four observers according to the Pipkin, Brumback, AO/Orthopaedic Trauma Association (OTA), Chiron, and New classifications. Each observer repeated his classifications again 1 month later to allow us to ascertain intraobserver reliability. To evaluate the universality of classifications, we characterized the percentage of hips that could be classified using the definitions offered in each classification. The kappa (κ) value was calculated to determine interrater and intrarater agreement. We then compared the classifications based on the combination of universality and interobserver and intraobserver reproducibility to determine which classifications might be recommended for clinical and research use. RESULTS: The universalities of the classifications were 99% (228 of 231, Pipkin), 43% (99 of 231, Brumback), 94% (216 of 231, AO/OTA), 99% (228 of 231, Chiron), and 100% (231 of 231, New). The interrater agreement was judged as almost perfect (κ 0.81 [95% CI 0.78 to 0.84], Pipkin), moderate (κ 0.51 [95% CI 0.44 to 0.59], Brumback), fair (κ 0.28 [95% CI 0.18 to 0.38], AO/OTA), substantial (κ 0.79 [95% CI 0.76 to 0.82], Chiron), and substantial (κ 0.63 [95% CI 0.58 to 0.68], New). In addition, the intrarater agreement was judged as almost perfect (κ 0.89 [95% CI 0.83 to 0.96]), substantial (κ 0.72 [95% CI 0.69 to 0.75]), moderate (κ 0.51 [95% CI 0.43 to 0.58]), almost perfect (κ 0.87 [95% CI 0.82 to 0.91]), and substantial (κ 0.78 [95% CI 0.59 to 0.97]), respectively. Based on these findings, we determined that the Pipkin and Chiron classifications offer near-complete universality and sufficient interobserver and intraobserver reproducibility to recommend them for clinical and research use, but the other classifications (Brumback, AO/OTA, and New) do not. CONCLUSION: Based on our findings, clinicians and clinician-scientists can use either the Pipkin or Chiron classification systems to classify femoral head fractures based on CT images, with equal confidence. It seems unlikely that any new classifications will substantially outperform these, and the other available systems either lacked sufficient universality or reproducibility to recommend them for general use. LEVEL OF EVIDENCE: Level III, diagnostic study.

Use of sugammadex is associated with reduced incidence and severity of postoperative nausea and vomiting in adult patients with obesity undergoing laparoscopic bariatric surgery: a post-hoc analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common but troublesome complication in patients who undergo laparoscopic bariatric surgery (LBS). Whether sugammadex use is related to the persistent decrease in the occurrence of PONV during postoperative inpatient hospitalization, which is critical for the rehabilitation of patients after LBS, remains unknown. METHODS: The study was based on a randomized controlled trial conducted in an accredited bariatric centre. A total of 205 patients who underwent LBS were included in the analysis. Univariate analysis and multivariable logistic regression model were used to identify the significant variables related to PONV. Then propensity score matching and inverse probability of treatment weighting (IPTW) were employed to compare outcomes between the sugammadex and neostigmine groups. The primary outcome was the incidence of PONV within 48 h after LBS. The secondary endpoints included the severity of PONV, time to first flatus, need for rescue antiemetic therapy, and water intake. RESULTS: The incidence of PONV was 43.4% (89/205) within the first 48 h after LBS. In multivariable analysis, sugammadex use (OR 0.03, 95% CI 0.01-0.09, P < 0.001) was an independent protective factor of PONV. After IPTW adjustment, sugammadex use was associated with lower incidence of PONV (OR 0.54, 95% CI 0.48-0.61, P < 0.001), postoperative nausea (PON) (OR 0.77, 95% CI 0.67-0.88, P < 0.001), and postoperative vomiting (POV) (OR 0.60, 95% CI 0.53-0.68, P < 0.001) within postoperative 48 h. The severity of PON as well as the incidence and severity of POV within the first 24 h were also lower in the sugammadex group (all P < 0.05). Reduced need for rescue antiemetic therapy within the first 24 h, increased water intake for both periods, and earlier first passage of flatus were observed in the sugammadex group (all P < 0.05). CONCLUSIONS: Compared with neostigmine, sugammadex can reduce the incidence and severity of PONV, increase postoperative water intake, and shorten the time to first flatus in bariatric patients during postoperative inpatient hospitalization, which may play a pivotal role in enhanced recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.aspx?proj=134893 , date of registration: October 25, 2021).

[Comparison of effect between internal fixation and total hip replacement in the treatment of displaced femoral neck fracture in middle age patients].

OBJECTIVE: To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years. METHODS: From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups. RESULTS: All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05). CONCLUSION: Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.

[Review of closed reduction techniques for femoral neck fracture].

For patients with femoral neck fractures who plan to undergo internal fixation, satisfied alignment of fracture ends is an important prerequisite for internal fixation stability and fracture healing. There are many reports on the reduction methods of displaced femoral neck fractures, which can be summarized into three categories:First, the solely longitudinal traction of lower limbs, supplemented by other manipulations such as rotation and compression; Second, the resultant force formed by the longitudinal traction of lower limbs and the lateral traction;the third is accomplished by vertical traction in the axis of femur with hip joint flexed. Each reduction method has its own advantages, but no single method can be applied to all fracture displacement. In this paper, some classical reduction techniques in the literatures are briefly reviewed. It is hoped that clinicians will not be limited to a certain reduction method, they should analyze the injury mechanism and fracture displacement process according to the morphology features and flexibly select targeted reduction methods to improve the success rate of closed reduction of femoral neck fracture.

[Assessment of the local blood supply when femoral neck fracture occurs:advances in the anatomy research and its clinical application].

The stability of internal fixation of femoral neck fractures can be obtained through surgical techniques, the configuration of screws and bone grafting, etc. However, the blood supply injury caused by fractures could not be completely reversed by the current medical management. Hence, the comprehensive evaluation of the residual blood supply of the femoral neck, to perioperatively avoid further iatrogenic injury, has become a hotspot. The anatomy of the extraosseous blood supply of the femoral neck has been widely reported, while its clinical application mostly involved the assessment of the medial circumflex femoral artery and retinacular arteries. However, further studies are needed to explore the prognosis of patients with these artery injuries, with different degrees, caused by femoral neck fractures. Direct observations of nutrient foramina in vivo are not possible with current clinical technologies, but it is possible to make reasonable preoperative planning to avoid subsequent femoral head necrosis based on the distribution features of nutrient foramina. The anatomy and clinical application studies of the intraosseous blood supply focused on the junction area of the femoral head and neck to probe the mechanism of femoral head necrosis. Thus, the intraosseous blood supply of other regions in the femoral neck remains to be further investigated. In addition, a blood supply evaluation system based on a three-level structure, extraosseous blood vessels, nutrient foramina, and intraosseous vascular network, could be explored to assist in the treatment of femoral neck fractures.

Relative efficacy of three different tendon repairs in complete flexor digitorum profundus laceration in Zone I: A randomized controlled study.

Hand flexor tendon injuries are common and biomechanically challenging to achieve good functional outcomes. Several approaches using the Pennington-modified Kessler repair technique have been attempted, but high-level evidence is still lacking. Here, we evaluated the relative efficacy of three versions of the Pennington-modified Kessler technique in repairing complete flexor digitorum profundus (FDP) laceration in Zone 1. We conducted a 2-year, single-center, double-blind, randomized clinical trial involving 85 patients with 105 digits enrolled between June 1, 2017 and January 1, 2019. Eligible participants were 20-60 years of age and underwent tendon repair in the acute phase for complete FDP laceration distal to the insertion of the superficial flexor tendon. The digits were randomized 1:1:1 to three treatment groups: (1) Pennington-modified Kessler repair; (2) Pennington-modified Kessler repair followed by circumferential tendon suture; or (3) Pennington-modified Kessler repair followed by circumferential epitenon suture. The primary endpoint was total active range of motion (TAROM) at 2 years after the initial surgery. The secondary endpoint was the reoperation rate. Compared with group 1, both techniques for peripheral suture were associated with a decrease in TAROM at 2 years after surgery. The total reoperation rates of the three groups were 11.4%, 18.2%, and 17.6%, and we found no significant differences among the three groups possibly due to the limited sample size. Unexpectedly, among participants with complete FDP laceration in Zone I, both circumferential-tendon and circumferential-epitenon sutures caused worsening of TAROM after 2 years. No conclusions can be drawn regarding reoperation rates among the groups. Level of evidence: Therapeutic level I.

PSKH1 affects proliferation and invasion of osteosarcoma cells via the p38/MAPK signaling pathway.

Malignant osteosarcoma (OS) is a tumor of bone and soft tissue that metastasizes early and has a high mortality rate. Protein serine kinase H1 (PSKH1), an autophosphorylating human protein serine kinase, controls the trafficking of serine/arginine-rich domain, with downstream effects on mRNA processing. It is also associated with tumor progression. However, how this protein contributes to OS progression and metastasis is unknown. The present study evaluated the potential effect of PSKH1 on proliferation of human OS cells. OS cell lines were used in Cell Counting Kit-8, colony formation, wound-healing and Transwell assays, to investigate cellular processes such as proliferation, migration and invasion and underlying molecular mechanisms. Expression of PSKH1 in OS tissue was significantly greater than in adjacent non-malignant tissue. PSKH1 knockdown inhibited the proliferation, migration and invasion of OS cells. Conversely, PSKH1 overexpression promoted proliferation of OS cells. PSKH1 upregulated phosphorylated-p38 in OS cells. Moreover, the p38 MAPK inhibitor SB203580 effectively blocked the tumor-promoting action of PSKH1. Furthermore, PSKH1 knockdown inhibited tumor growth and metastasis in vivo. In conclusion, these findings suggested that PSKH1 promoted OS proliferation, migration and invasion. Thus, PSKH1 may serve an oncogenic role in the development of human OS.

Radiologists with assistance of deep learning can achieve overall accuracy of benign-malignant differentiation of musculoskeletal tumors comparable with that of pre-surgical biopsies in the literature.

PURPOSE: The purpose of this study was to assess if radiologists assisted by deep learning (DL) algorithms can achieve diagnostic accuracy comparable to that of pre-surgical biopsies in benign-malignant differentiation of musculoskeletal tumors (MST). METHODS: We first conducted a systematic review of literature to get the respective overall diagnostic accuracies of fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in differentiating between benign and malignant MST, by synthesizing data from the articles meeting our inclusion criteria. To compared against the accuracies reported in literature, we then invited 4 radiologists, respectively with 2 (A), 6 (B), 7 (C), and 33 (D) years of experience in interpreting musculoskeletal MRI to perform diagnostic tests on our own dataset (n = 62), with and without assistance of a previously developed DL algorithm. The gold standard for benign-malignant differentiation was histopathologic confirmation or clinical/radiographic follow-up. RESULTS: For FNAB, a meta-analysis containing 4604 samples met the inclusion criteria, with the overall diagnostic accuracy reported to be 0.77. For CNB, an overall accuracy of 0.86 was derived by synthesizing results from 7 original research articles containing a total of 587 samples. On our internal MST dataset, the invited radiologists, respectively, achieved diagnostic accuracies of 0.84 (A), 0.89 (B), 0.87 (C), and 0.90 (D), with the assistance of DL. CONCLUSION: Use of DL algorithms on musculoskeletal dynamic contrast-enhanced MRI improved the benign-malignant differentiation accuracy of radiologists to a level comparable to that of pre-surgical biopsies. The developed DL algorithms have a potential to lower the risk of miss-diagnosing malignancy in radiological practice.

Reoperation rate and implants' position variation features of displaced femoral neck fractures with sliding compression or length-stable fixation in young and middle-aged population.

INTRODUCTION: Sliding compression fixation and length-stable fixation are two basic internal fixation concepts in the treatment of displaced femoral neck fractures. In this study, we aimed to compare the reoperation rates for different methodologies of internal fixation for femoral neck fractures in young and middle-aged population. MATERIALS AND METHODS: This a retrospective study. A total of 215 patients with displaced femoral neck fractures treated with cannulated screw fixation were enrolled and divided into the sliding compression and length-stable groups according to the fixation pattern. The occurrence of and reason for revision surgery within one year were recorded. Forty-five patients with complete CT data (including CT scanning on the first postoperative day and at the last follow up) were selected from the total sample. A newly established computerized image processing method was used to evaluate variations in the spatial location of screws. RESULTS: The reoperation rate was significantly higher in the length-stable group (23.8%) than in the sliding compression group (7.3%). The rate of revision surgery due to nonunion was also higher in the length-stable group (11.4%) than in the sliding compression group (1.8%). However, no significant difference was observed in terms of joint penetration or soft tissue irritation. The sliding compression group (6.58 ± 3.18 mm) showed higher femoral neck shortening than length-stable group (4.16 ± 3.65 mm). When analyzing the spatial variations, a significantly greater screw withdrawal distance was observed in the sliding compression group than in the length-stable group, but with a smaller rotation angle. CONCLUSION: Length-stable internal fixation of displaced femoral neck fractures may lead to an increased reoperation rate in young and middle-aged population. TRIAL REGISTRATION: Name of the registry: Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2000032327. Trial registration date: 2020-4-26.

Three-dimensional computed tomography mapping and clinical predictive factors for morphologic characterization of displaced femoral neck fractures.

Background: This study aimed to define the distribution and frequency of fracture lines and bone defects in displaced femoral neck fractures (DFNFs) using a three-dimensional (3D) mapping technique, and to investigate the factors associated with the area of bone defects in patients with DFNFs. Methods: The data of 256 adult patients with DFNFs were retrospectively reviewed. Multiplanar reconstructions of the DFNFs were made using computed tomography (CT) images, and the DFNF fragments were virtually reduced to match a 3D model of the femoral neck. Subsequently, 3D mapping was performed by graphically superimposing all of the fracture lines and bone defects onto a femoral neck template. The 3D mappings were independently examined by two orthopedic surgeons, and the interobserver agreement was analyzed. For intraobserver analysis, one of the surgeons measured the mappings twice more, and the intraclass correlation coefficients (ICCs) were calculated. A linear regression analysis was conducted to explore bone defect area-related factors. Results: The cohort comprised 141 (55%) patients with left hip injuries and 115 (45%) patients with right hip injuries. On the 3D maps, the dense zones of the fracture lines were largely observed from the superior to the posterior part of the femoral neck, while the dense zone of the bone defect was primarily concentrated in the posterior part of the femoral neck. Only a few dense zones were located in the anterior and inferior parts of the femoral neck. An overlapping region between the fracture line and the bone defect was located in the 2.5th to 4.5th (5th) part of the 1/10 of the superior (posterior) femoral neck length. Both the fracture line and bone defect mapping techniques had good intra- and inter-observer reliability, with ICCs of 0.879 (0.977) and 0.780 (0.974), respectively. Garden type and age were positively correlated with bone defects, while simplified AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification was negatively associated with bone defects. Conclusions: The fracture lines and bone defects of the DFNFs were mainly located in the superior and posterior parts of the femoral neck, while an overlapping region was observed in the subcapital area of the femoral neck. 3D mapping is a reliable method for searching for DFNF features, and separately studying fracture lines and bone defects can further elucidate the morphology of these fractures. Bone defects in patients with DFNFs were associated with Garden type, simplified AO/OTA classification, and age.

Association between Weitbrecht's Retinaculum Injury and Femoral Head Necrosis in Femoral Neck Fractures.

OBJECTIVE: To investigate associations between femoral head necrosis (FHN) and injury to the retinaculum of Weitbrecht in patients with femoral neck fractures who had undergone initial trials of either closed reduction or direct open reduction. METHODS: This prospective observational study included 110 patients with displaced femoral neck fractures admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and Shanghai Tongji Hospital between January 2008 and May 2017. Among these, 25 patients underwent initial closed reductions, and 85 patients underwent an open reduction directly. Watson-Jones anterolateral approach was used during the surgery for injury to the retinaculum of Weitbrecht, and FHN was assessed as a surgical outcome. The severity of injury to the retinaculum of Weitbrecht was evaluated using a scoring system developed by our surgical team. Follow-up was at least 24 months. RESULTS: The initial closed reduction treatment group had significantly higher total scores of injury to the retinaculum of Weitbrecht (6.24 ± 2.20 vs 4.62 ± 2.12, p = 0.009) compared to the open reduction group. High total scores were significantly associated with initial trials of closed reduction treatment, especially for the broken and released injury to the superior and anterior retinacula (both p = 0.01). Twenty-six patients experienced FHN postoperatively, with mean onset time of 19.42 ± 3.87 months. FHN was significantly associated with the severity of injury to the retinaculum of Weitbrecht (p < 0.001) at the superior, anterior, and inferior retinacula. FHN was significantly associated with injury to the retinaculum of Weitbrecht in females. CONCLUSIONS: Femoral neck displacement in patients treated initially with closed reduction is associated with subsequent injury to the retinaculum of Weibrecht, which may lead to FHN. Severity of injury to the retinaculum of Weibrecht may be used as a biomarker to evaluate bone necrosis in patients with femoral neck fractures.

A quantitative study of bone defects in displaced femoral neck fractures based on virtual reduction techniques.

BACKGROUND: Bone defects in femoral neck fractures are strongly associated with the prognosis after internal fixation. However, qualitative analysis of bone defects in femoral neck fractures has already been performed, quantitative studies have not been reported. In this study, we aimed to systematically analyse the morphological characteristics of bone defects in patients with femoral neck fractures using computed tomography (CT) images combined with computer image analysis techniques. METHODS: Four hundred and sixty-nine patients with femoral neck fractures from January 2014 to December 2018 at two grade A tertiary hospitals were included. Models were created in Mimics software based on CT images collected within 1 week after injury and then imported into 3-matic software for virtual reduction. The volume of the bone defect (VBD), maximum defect thickness (MDT), extent of the bone defect region (EBDR) , main defect quadrant (MDQ), collapse type and fracture classification were calculated and recorded. RESULTS: The EBDR, collapse type and MDT all had a significant positive effect on the VBD (P <0.05), with a more significant effect at higher quantiles. Age also had a significant positive effect on the VBD (P < 0.05), but its effect was more pronounced at lower quantiles. Compared to non-subcapital fractures, subcapital fractures had a positive effect on the VBD only at the 50 and 75% quantiles (P < 0.01). The female sex had a significant negative effect on the VBD compared to the male sex (P < 0.05). CONCLUSION: This study established a reliable computer image processing method for quantitative analysis of the VBD in femoral neck fractures and revealed that all patients with femoral neck fractures had bone defects, which can occur at any part of the femoral neck. The EBDR, MDT, collapse type, and patient age and sex were all important risk factors for the extent of the defect and should be taken into account in surgical planning.

Therapeutic Effect of Biejiaxiaozheng Pills on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through the NF-κB/Nrf2 Pathway.

AIMS: To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-ß, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-ß, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. RESULTS: In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. CONCLUSION: Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

A retrospective cohort study on prevalence of postoperative complications in comminuted patellar fractures: comparisons among stabilized with Cannulated-Screw, Kirschner-Wire, or Ring-Pin Tension Bands.

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.

Dexmedetomidine attenuates sevoflurane­induced neurocognitive impairment through α2­adrenoceptors.

It has been reported that sevoflurane induces neurotoxicity in the developing brain. Dexmedetomidine is an α2 adrenoceptor agonist used for the prevention of sevoflurane­induced agitation in children in clinical practice. The aim of the present study was to determine whether dexmedetomidine could prevent sevoflurane­induced neuroapoptosis, neuroinflammation, oxidative stress and neurocognitive impairment. Additionally, the involvement of α2 adrenoceptors in the neuroprotective effect of dexmedetomidine was assessed. Postnatal day (P)6 C57BL/6 male mice were randomly divided into four groups (n=6 in each group). Mice were pretreated with dexmedetomidine, either alone or together with yohimbine, an α2 adrenoceptor inhibitor, then exposed to 3% sevoflurane in 25% oxygen. Control mice either received normal saline alone or with sevoflurane exposure. Following sevoflurane exposure, the expression of cleaved caspase­3 was detected by immunohistochemistry in hippocampal tissue sections. In addition, the levels of tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß, IL­6 and malondialdehyde, as well as superoxide dismutase (SOD) activity in the hippocampus were measured. At P35, the learning and memory abilities were assessed in each mouse using a Morris water maze test. Dexmedetomidine significantly decreased the expression of activated caspase­3 following sevoflurane exposure. Moreover, dexmedetomidine significantly decreased the levels of TNF­α, IL­1ß and IL­6 in the hippocampus. SOD activity also increased in a dose­dependent manner in dexmedetomidine­treated mice. MDA decreased in a dose­dependent manner in dexmedetomidine­treated mice. Lastly, sevoflurane­induced learning and memory impairment was reversed by dexmedetomidine treatment. By contrast, co­administration of yohimbine significantly attenuated the neuroprotective effects of dexmedetomidine. These findings suggested that dexmedetomidine exerted a neuroprotective effect against sevoflurane­induced apoptosis, inflammation, oxidative stress and neurocognitive impairment, which was mediated, at least in part, by α2 adrenoceptors.

Integrin-Linked Kinase Is Involved In the Proliferation and Invasion of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an aggressive type of cancer with high mortality rate in China, largely due to its high invasive and metastatic potential. The purposes of this study are to investigate the potential molecular mechanisms behind the aggressive nature of ESCC and search for new prognostic biomarkers. By employing the quantitative proteomic based strategy, we compared the proteomic profile between three ESCC samples and paired adjacent tissues. After bioinformatics analysis, four candidate proteins were validated in thirteen paired patient samples. Further validation of the key candidate, integrin-linked kinase (ILK), was carried out in one hundred patient samples. The specific inhibitor compound 22 (cpd22) was used to assess the influence of ILK to ESCC cell motility and invasiveness by applying wound-healing and transwell assay. Western blot analysis was performed to elucidate the signaling pathways involved in ILK-mediated ESCC invasion. Total 236 proteins were identified by proteomic analysis. Bioinformatics analysis suggested a key role of the collagen/integrin/ILK signaling pathway during ESCC progression. Further validation indicated that ILK is overexpressed in ESCC tissues and is correlated with poor patient prognosis. Inhibition of ILK kinase activity suppresses proliferation and blocks invasion and migration of ESCC cells. Signaling pathway analysis revealed that ILK regulates AKT phosphorylation on Ser473 but not GSK-3ß on Ser9 to promote proliferation and motility of ESCC cells. In conclusion, our results indicated that ILK may play a crucial role in ESCC invasion and metastasis and may serve as a prognostic biomarker and therapeutic target for ESCC.