Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Three-dimensional printing combined with open reduction and internal fixation versus open reduction and internal fixation in the treatment of acetabular fractures: A systematic review and meta-analysis.

PURPOSE: This meta-analysis compared the clinical outcome of three-dimensional (3D) printing combined with open reduction and internal fixation (ORIF) to traditional ORIF in the treatment of acetabular fractures. METHODS: We searched the Cochrane Library, PubMed, Embase, VIP database, CNKI, and Wanfang database with keywords "acetabular fracture", "3D printing", "three-dimensional printing", "open reduction and internal fixation", "Acetabulum", "Acetabula" from January 2000 to March 2020. Two reviewers independently selected articles, extracted data, assessed the quality evidence and risk bias of included trials using the Cochrane Collaboration' s tools and/or Newcastle-Ottawa scale. When the two analysts had different opinions, they would ask the third analyst for opinion. Randomized controlled trials or retrospective comparative studies of 3D printing combined with ORIF (3D printing group) versus traditional ORIF (conventional group) in the treatment of acetabular fractures were selected. The data of operation time, intraoperative blood loss, intraoperative fluoroscopy times, incidence of complications, excellent and good rate of Matta score for reduction, and excellent and good rate of hip function score were extracted. Stata14.0 statistical software was used for data analysis. RESULTS: Altogether 9 articles were selected, including 5 randomized controlled trials and 4 retrospective studies. A total of 467 patients were analyzed, 250 in the conventional group, and 217 in the 3D printing group. The operation time in the 3D printing group was less than that in the conventional group and the difference was statistically significant (standardized mean difference (SMD) = -1.19, 95% CI: -1.55 to -0.82, p < 0.05). The intraoperative bleeding volume of the 3D printing group was significantly lower than that of the conventional group (SMD = -1.08, 95% CI: -1.65 to -0.51, p < 0.05). The fluoroscopy times were less in the 3D printing group than in the conventional group and the difference was statistically significant (SMD = -1.64, 95% CI: -2.35 to -0.93, p < 0.05). The total incidence of complications in the 3D printing group was significantly lower than that in the conventional group (OR = 0.43, 95% CI: 0.24-0.79, p < 0.05). There was no significant difference in the excellent and good rate of Matta score for reduction between the two groups (OR = 0.60, 95% CI: 0.34-1.06, p > 0.05). There was no significant difference in the excellent and good rate of hip function score at the end of postoperative follow-up between the two groups (OR = 0.84, 95% CI: 0.46-1.56, p > 0.05), but the follow-up time varies from 6 months to 40 months. CONCLUSION: Compared with traditional ORIF, 3D printing combined with ORIF has certain advantages in terms that 3D printing not only helps surgeons to understand acetabular fractures more intuitively, but also effectively reduces operation time, intraoperative blood loss, intraoperative fluoroscopy times, and postoperative complications. However, there were no significant differences in the excellent and good rate of Matta score for reduction and the excellent and good rate of hip function score at the end of follow-up.

Twenty Years Development of Tibial Cortex Transverse Transport Surgery in PR China.

Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique. Based on the law of tension-stress, its primary function is to rebuild microcirculation which can relieve ischemic symptoms and promote wound healing. It has received more and more scholars' attention and has experienced a series of changes for 20 years since it entered PR China. The mechanisms involved have gradually become clear, such as the reconstruction of the polarization balance of macrophages, the promotion of vascular tissue regeneration, and the mobilization and regulation of bone marrow-derived stem cells. TTT technique is mainly used in the treatment of chronic ischemic diseases of the lower extremities. It has recently been successfully used in the treatment of primary lymphedema of the lower extremities. A series of improvements have been made in the external fixator's style, the size of skin incision and osteotomy, and distraction method. For example, the annular external fixator has been redesigned as a unilateral external fixator, and accordion technology has been introduced. For distraction methods after surgery, there was no uniform standard in the past. The technique can also be used in combination with other treatments to achieve better effects, such as interventional therapy, negative pressure sealed drainage, 3D printing technology, traditional Chinese medicine. Nevertheless, the surgery may bring some complications, such as secondary fracture, nail infection, skin necrosis at the surgical site, etc. Reports of complications and doubts about the technique have made the TTT technique controversial. In 2020, the relevant expert consensus was published with treatment and management principles, which might guide the better application and development of this technique.

[Progress on knee cartilage repair by knee joint distraction].

Knee joint distraction is a new technology for the treatment of knee osteoarthritis in recent years. It could reduce knee pain and improve knee function, which is inseparable from the role of cartilage repair. The mechanism and influencing factors of knee joint distraction in repairing cartilage are the focus of current research. In this paper, the author reviewed literature and found that knee joint distraction could reduce knee joint load and provide a appropriate mechanical environment for cartilage repair, and it is resulting hydrostatic pressure fluctuation in the knee joint not only helps cartilage to absorb nutrients, but also promotes cartilage formation genes and inhibits cartilage matrix degrading enzyme gene expression. In addition, knee joint distraction creates conditions for synovial mesenchymal stem cells to be collected to cartilage injury, and improves ability of synovial mesenchymal stem cells to proliferate and differentiate into a chondrogenic lineage. Knee joint distraction could reduce inflammatory reaction and cartilage injury of knee joint by reducing content of inflammatory factors and inhibiting expression of inflammatory genes. At present, it is known that the factors affect repair of cartilage by knee joint distraction include, increasing weight-bearing activity and height and time of distraction is helpful for cartilage repair, male patients and patients with higher severity of knee osteoarthritis have better cartilage repair effect after knee joint distraction.The better efficacy of cartilage repair on the first year after knee joint distraction predicts a higher long-term survival rate of knee joint distraction with knee preservation. However, the research on the above hot spots is only at the initial stage and further exploration is still needed, in order to better guide clinical application of knee joint distraction.

Internal Fixation versus Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fractures in the Elderly: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the clinical efficacy of internal fixation versus hemiarthroplasty in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: A search was conducted in PubMed, Web of Science, Embase, and Cochrane Library databases up to April 2020. The present study compared internal fixation and hemiarthroplasty in the treatment of unstable intertrochanteric fractures in the elderly. RevMan5.3 software provided by the International Cochrane Group was used for the meta-analysis. To compare the differences in the operation time, intraoperative bleeding, length of hospital stay, superficial infection, Harris hip score, mortality within 1 year, mortality within 2 years, reoperation, incidence of deep venous thrombosis (DVT), partial weight-bearing time, non-union, and implant-related complications between an internal fixation group and an hemiarthroplasty group. RESULTS: A total of 1300 patients were included in nine studies. The results showed that the operation time (MD = -18.09, 95% CI: -27.85--8.34, P = 0.0003), intraoperative bleeding (MD = -195.31, 95% CI: -244.8--147.74, P < 0.0001), implant-related complications (MD = 3.83, 95% CI: 1.74-8.45, P = 0.0008), and partial weight-bearing time (MD = 17.21, 95% CI: 1.63-32.79, P = 0.03) have statistical significance. However, there is not statistical significance for the Harris hip joint function scale (HHS) (MD = 5.60, 95% CI: -1.13-12.33, P = 0.10), DVT (MD = 1.02, 95% CI: 0.45-2.27, P = 0.97), length of hospital stay (MD = -1.08, 95% CI: -2.82-0.66, P = 0.22), superficial Infection (OR = 0.92, 95% CI: 0.43-1.98, P = 0.89), mortality within 1 year (OR = 0.95, 95% CI: 0.61-1.48, P = 0.81), mortality within 2 years (OR = 0.93, 95% CI: 0.61-1.43, P = 0.75), reoperation (MD = 1.80, 95% CI: 0.64-5.04, P = 0.26), and non-union (OR = 1.20, 95% CI: 0.48-3.03, P = 0.70). The result of the subgroup analysis showed no significant differences between the less than 2 years follow-up and the 2 years or more follow-up group. The only difference was for the Harris hip score: the internal fixation group was superior to the hemiarthroplasty group in the less than 2 years subgroup analysis, while there was no difference between the internal fixation group hemiarthroplasty group in the 2 years or more subgroup analysis. CONCLUSION: Compared with the internal fixation group, those in the hemiarthroplasty group could carry out weight-bearing training early and implant-related complications were reduced, but it requires longer operation time and there is greater intraoperative blood loss. There is no difference in mortality, the incidence of DVT, non-union, HHS, reoperation, length of hospital stay, and superficial infection. Hemiarthroplasty may be a better choice for unstable intertrochanteric fractures in the elderly.

Conservative Treatment or Surgical Treatment: A Case Report and Literature Review of Multiple Fractures of the Lower Extremities in a Child with Insensitivity to Pain.

Congenital pain insensitivity is a rare genetic disease and its clinical manifestations are many. In orthopaedics, common complications of this disease include painless fracture and Charcot's arthropathy. We followed up a case of multiple fractures of the lower extremity in two years, during which time he came to the clinic for five painless fractures of the lower extremity in a total of six parts. A mutation was found on the NTKRI gene (chr1:156813923(hg19), NM_001007792.1: c.1221938C > T). We have developed a combination of surgery and conservative treatments for his condition, focusing on the mental state of the child and considering comprehensive treatment to be the best option for this type of patient. Occult fractures caused by pain insensitivity are often treated only as fractures, however their complications require routine examination and cleaning, suitable protective shoes, splint fixation, stretching, guided exercise planning, and early treatment of injuries. Due to the risk of fracture in the future, it is important that parents pay attention to the behavior and psychology of the child, such as not letting the child participate in exercise with a risk of injury, protective measures while playing, engaging in psychological counseling, and inducing interest in mental activity. These interventions will play a very important role in preventing the recurrence of fracture.

[Progress on diagnosis and treatment of crown dens syndrome].

Crowned dens syndrome(CDS) is a major imaging manifestation of "coronary" calcified deposits around the odontoid, with pain, stiffness, fever, and even cervical cord compression in the upper head and neck. It was first described by Bouvet et al. in 1985, and the onset was generally thought to be caused by crystal deposition. The clinical manifestations of CDS are often similar to meningitis and often accompanied by an increase in inflammatory markers in the blood. As a result, it is very easy to obtain missed diagnosis and misdiagnosis, and it is clinically prone to obtain wrong or unnecessary treatment. At present, the diagnosis of CDS is based on the imaging findings in CT as a "golden standard". NASIDs drugs and corticosteroids are the main treatment. The prognosis is also generally good, and the imaging findings of the patients with the disease disappear completely within 3 months.