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Abstract Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.

Two new three-dimensional organic–inorganic hybrid crystalline materials, [(Ade)2 CdCl4] (1) and [(Ade)2 CdBr4] (2), were obtained by the slow evaporation of adenine (Ade) and cadmium chloride in aqueous solution at room temperature with hydrochloric acid and hydrobromic acid used as halogen sources. The structural, thermal, optical, and electrical properties were characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, variable-temperature–variable-frequency dielectric constant analysis, and electrochemical tests. With increasing the substitution of Cl by Br, the composition of the material changed and the space group shifted from P-1 to P21/m, with a significant blue-shift in the fluorescence emission. Changing the temperature induced the deformation of the three-dimensional framework structure formed by hydrogen bonding interactions, leading to dielectric anomalies. Cyclic voltammetry tests showed the good reversibility of the electrolysis process. The structural diversity of the complexes was realized by modulating the halogen composition, and a new method for designing novel organic–inorganic hybrids with controllable photoelectric functionality was proposed.

Abstract Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of β3- or β2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of β2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in β3-AR knockout mice. Moreover, β3- and β2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

In order to improve the classification accuracy of loudspeaker abnormal sounds, this paper proposes a method based on time-varying specific loudness weighted by energy entropy and principal component analysis. This method simulates human auditory perception mechanism to process loudspeaker sound response signal to obtain more effective features. The human hearing system can be divided into many parallel and functionally independent conduction pathways according to frequency. The energy of the acoustic signal in each pathway can be discerned. Therefore, the time-varying specific loudness is calculated firstly to build the quantitative correlation of loudspeaker’s acoustic response signals and human hearing sensations. Each sub band loudness is weighted by energy entropy to highlight the acoustic strength variation with time and frequency. Then, important features are extracted by two dimensional-principal component analysis (2D-PCA). Finally, the whale optimization algorithm-least squares support vector machine (WOA-LSSVM) is adopted for classification. Visual analysis of the extracted features shows that this method can extract loudspeaker response signal features with better discriminability. Classification experimental results show that the average accuracy of this method reached 98.4%, which is higher than the classification method based on traditional time-frequency domain statistical features. The loudspeaker abnormal sound classification method in this paper simulates human auditory perception to extract features and is able to improve classification accuracy and automation effectively.

Abstract The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel “don’t eat me” signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

The synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted considerable attention in the field of cancer therapy because of its excellent anti-tumor effect. This work provides a novel pH/NIR responsive therapeutic nanoplatform, IrO2@ZIF-8/BSA-FA (Ce6), producing a synergistic effect of PTT-PDT in the treatment of osteosarcoma. Iridium dioxide nanoparticles (IrO2 NPs) with exceptional catalase-like activity and PTT effects were synthesized by a hydrolysis method and decorated with zeolitic imidazolate framework-8 (ZIF-8) shell layer to promote the physical absorption of Chlorin e6 (Ce6), and further functionalized with bovine serum albumin-folate acid (BSA-FA) for targeting tumor cells. The IrO2@ZIF-8/BSA-FA nanocomposite indicated an outstanding photothermal heating conversion efficiency of 62.1% upon laser irradiation. In addition, the Ce6 loading endows nanoplatform with the capability to induce cell apoptosis under 660 nm near-infrared (NIR) laser irradiation through a reactive oxygen species (ROS)-mediated mechanism. It was further testified that IrO2@ZIF-8/BSA-FA can function as a catalase and convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2) to improve the local oxygen pressure under the acidic tumor microenvironment (TME), which could subsequently amplified PDT-mediated ROS cell-killing performance via relieving hypoxia microenvironment of tumor. Both in vitro and in vivo experimental results indicated that the nanomaterials were good biocompatibility, and could remarkably achieve tumor-specific and enhanced combination therapy outcomes as compared with the corresponding PTT or PDT monotherapy. Taken together, this work holds great potential to design an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Osteosarcoma often presents the low response to chemotherapy, which brings difficulties to the treatment. Recently, it has become a new idea to use photothermal effect and Fenton/Fenton-like reaction to treat tumors or enhance the killing effect of chemotherapy drugs. We developed an iron-containing nanomaterial SiO2@PDA/Fe3+-FA (PDA: polydopamine; FA: folate) to treat chemotherapy-insensitive osteosarcoma. The nanomaterial has been proven to have: (1) high drug delivery efficiency (doxorubicin and cisplatin: 21.25% and 23.80% respectively), (2) precise release of drugs in pH response, (3) good biocompatibility, (4) effective tumor targeting (8 h after injection), and (5) satisfactory photothermal efficiency (photothermal conversion efficiency: 57.63%). Of note, nanomaterial containing Fe3+ ions can activate the Fenton-like reaction to generate reactive oxygen species (ROS) and induce apoptosis of drug-insensitive osteosarcoma cells. In addition, nanomaterial can also enhance the killing effect of cisplatin on drug-insensitive osteosarcoma. The activation of Fenton-like reaction and the recovery of cisplatin function by nanomaterials are significantly enhanced under low temperature photothermal conditions. The in vitro and in vivo experiments showed that SiO2@PDA/Fe3+-FA could be loaded with appropriate chemotherapy drugs and could be used as an effective means of synergistic therapy for drug-resistant tumors in combination with near infrared ray (NIR) irradiation.

Objective To investigate whether four‐screw fixation in rhombic configuration could improve the clinical outcomes and decrease the complication rate compared with three‐screw fixation in inverted triangle configuration in elderly patients with nondisplaced femoral neck fractures. Method From January 2018 to January 2019, 91 elderly patients with nondisplaced femoral neck fractures who were treated with a cannulated screw system were reviewed retrospectively. The inverted triangle configuration was applied in 51 patients and rhombic configuration in 40 patients. The demographic and perioperative information of the patients were extracted from medical records and surgical records. Variables including incision size, surgical blood loss, surgical time, fluoroscopy time, hospital stays, fracture union time, postoperative visual analogue scale (VAS) scores, and complications were compared between the two groups. Also, Harris hip score at the final follow‐up was used to evaluate the functional outcomes. Results All patients were followed up from 24 to 36 months, with an average of 29.75 months. The average age of patients was 72.37 ± 7.16 years. No significant differences were found between the two groups with regard to patients' age, gender, affected side, Garden classification, Pauwels classification and comminution of posterior wall (P > 0.05). We found shorter incision size (P

A novel hydrogen-bonded supramolecular crown-ether-based inclusion compound, [(DL-α-Phenylglycine)(18-crown-6)]+[(CoCl4)0.5]−(1), was obtained via evaporation in a methanolic solution at room temperature using DL-α-phenylglycine, 18-crown-6, cobalt chloride (CoCl2), and hydrochloric acid. Its structure, thermal properties, and electrical properties were characterized via elemental analysis, single-crystal X-ray diffraction, variable-temperature infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and variable temperature–variable frequency dielectric constant testing. The compound was a monoclinic crystal system in the C2 space group at low temperature (100 K) and room temperature (293 K). Analysis of the single crystal structure showed that [(CoCl4)0.5]− presented an edge-sharing ditetrahedral structure in the disordered state, while the protonated DL-α-phenylglycine molecule in the disordered state and intramolecular hydroxyl group (-OH) underwent dynamic rocking, causing a significant stretching motion of the O-H···Cl-type one-dimensional hydrogen bond chain. This resulted in dielectric anomalies in the three axes of the crystal, thus showing significant dielectric anisotropy.

Introduction: Mitochondria-targeted low-temperature photothermal therapy (LPTT) is a promising strategy that could maximize anticancer effects and overcome tumor thermal resistance. However, the successful synthesis of mitochondria-targeted nanodrug delivery system for LPTT still faces diverse challenges, such as laborious preparations processes, low drug-loading, and significant systemic toxicity from the carriers.Methods: In this study, we used the tumor-targeting folic acid (FA) and mitochondria-targeting berberine (BBR) derivatives (BD) co-modified polyethylene glycol (PEG)-decorated graphene oxide (GO) to synthesize a novel mitochondria-targeting nanocomposite (GO-PEG-FA/BD), which can effectively accumulate in mitochondria of the osteosarcoma (OS) cells and achieve enhanced mitochondria-targeted LPTT effects with minimal cell toxicity. The mitochondria-targeted LPTT effects were validated both in vitro and vivo.Results:In vitro experiments, the nanocomposites (GO-PEG-FA/BD) could eliminate membrane potential (ΔΨm), deprive the ATP of cancer cells, and increase the levels of reactive oxygen species (ROS), which ultimately induce oxidative stress damage. Furthermore, in vivo results showed that the enhanced mitochondria-targeted LPTT could exert an excellent anti-cancer effect with minimal toxicity.Discussion: Taken together, this study provides a practicable strategy to develop an ingenious nanoplatform for cancer synergetic therapy via mitochondria-targeted LPTT, which hold enormous potential for future clinical translation.

Bone metastases, as one of the common types of metastatic tumors, have a great impact on the survival period and quality of life of patients. Bone metastases are usually characterized by bone destruction. Skeletal related events caused by bone destruction often lead to pain, pathological fractures and even paralysis. In this review, we provide a detailed explanation of bone metastases from the epidemiology, clinical features, pathogenesis, and recently developed clinical treatment viewpoints. We concluded that the incidence of bone metastases is increasing gradually, with serious clinical symptoms, complex pathogenesis and diverse clinical treatment. Tumor cells, immune cells, osteoblasts/osteoclasts and other cells as well as cytokines and enzymes all play a key role in the pathogenesis of bone metastases. We believe that the future treatment of bone metastases will be diversified and comprehensive. Some advanced technologies, such as nanomedicine, could be used for treatment, but this depends on understanding how disease occurs. With the development of treatment, the survival time and quality of life of patients will be improved.

Abstract Background Although lower temperature (

Abstract Background Several studies have demonstrated a relationship between the posterior tibial slope (PTS) and meniscal tears in adults. However, little is known about the association between the PTS of the adolescents and medial meniscal tears (MMT). The purpose of this study was to evaluate the association between the PTS and MMT in adolescents, and to determine the optimal cut-off values of PTS for discriminating between the MMT and the control groups. Methods Between January 2018 and January 2020, a retrospective case-control study was performed. In this study, isolated MMT adolescent patients with no ligamentous injuries were matched by age and sex to a control group of radiologically normal images. The PTS was defined as the angle between the perpendicular line to proximal tibial cortex (PTC) and the tangent line along the tibial plateau. Then, both the medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS) were measured by plain radiographs on the lateral views. In addition, the optimal cut-off values of PTS were determined by the receiver operating characteristic (ROC) curve analysis. Results A total of seventy-two patients who met the inclusion criteria were enrolled in the final analysis (36 patients with isolated MMT, 36 controls). The MPTS was greater in the knees with isolated MMT (10.7° ± 2.1°) than that of the control group (8.8° ± 1.7°), showing significant difference (P0.05). In the ROC curve analysis, the calculated cutoff value of the MPTS discriminating between the groups was 10.3°, with a sensitivity of 73.3% and specificity of 78.9%. Conclusions This study demonstrated that steep MPTS is associated with MMT, and MPTS≥10.3° was identified to be a risk factor for MMT in adolescents.

Abstract Objective We aimed to evaluate risk factors and develop a nomogram for reoperation after internal fixation of nondisplaced femoral neck fractures (FNFs) in elderly patients. Methods We conducted a retrospective study involving a total of 255 elderly patients who underwent closed reduction and internal fixation with cannulated screw system for nondisplaced FNFs between January 2016 and January 2019. We collected data on demographics, preoperative radiological parameters, surgery, serum biochemical markers, and postoperative rehabilitation. In addition, we performed univariate and multivariate logistic regression analyses to determine independent risk factors for reoperation, and then developed a nomogram to assess the risks of reoperation. Besides, discriminative ability, calibration, and clinical usefulness of the nomogram were evaluated using the concordance index (C-index), the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA), respectively. We employed bootstrap method to validate the performance of the developed nomogram. Results Our analysis showed that among the 255 patients, 28 (11.0%) underwent reoperation due to osteonecrosis of the femoral head (14 cases), mechanical failure (8 cases) or nonunion (6 cases). All of the 28 patients underwent conversion surgery to arthroplasty. The multivariate logistic regression analysis demonstrated that preoperative posterior tilt angle ≥ 20°, Pauwel’s III type, younger patients, preoperative elevated levels of alkaline phosphatase (ALP), preoperative hypoalbuminemia, and early postoperative weight-bearing were independent risk factors for reoperation. In addition, the C-index and the bootstrap value of the developed nomogram was 0.850 (95% CI = 0.803–0.913) and 0.811, respectively. Besides, the calibration curve showed good consistency between the actual diagnosed reoperation and the predicted probability, while the DCA indicated that the nomogram was clinically valuable. Conclusions Our analysis showed we successfully developed and validated a nomogram for personalized prediction of reoperation after internal fixation of nondisplaced FNFs in elderly patients. This model would help in individualized evaluation of the need for reoperation and inform strategies aimed at eliminating the need for the reoperation.

The importance of reactive oxygen species (ROS) in the occurrence and development of orthopaedic related diseases is becoming increasingly prominent. ROS regulation has become a new method to treat orthopaedic related diseases. In recent years, the application of nanomaterials has become a new hope for precision and efficient treatment. However, there is a lack of reviews on ROS-regulated nanomaterials for orthopaedic related diseases. Based on the key significance of nanomaterials for the treatment of orthopaedic related diseases, we searched the latest related studies and reviewed the nanomaterials that regulate ROS in the treatment of orthopaedic related diseases. According to the function of nanomaterials, we describe the scavenging of ROS related nanomaterials and the generation of ROS related nanomaterials. In this review, we closely integrated nanomaterials with the treatment of orthopaedic related diseases such as arthritis, osteoporosis, wound infection and osteosarcoma, etc., and highlighted the advantages and disadvantages of existing nanomaterials. We also looked forward to the design of ROS-regulated nanomaterials for the treatment of orthopaedic related diseases in the future.

Chemodynamic therapy (CDT) is an effective anti-tumor method, while CDT alone cannot achieve a good therapeutic effect. Moreover, the overexpression of glutathione (GSH) in tumor cells dramatically limits the efficiency of CDT. Here, we proposed a hydrogel co-loading SO2 prodrug and FeGA nanoparticles (NPs) for enhancing CDT by photothermal-triggered SO2 gas therapy (FBH) system by mixing benzothiazolyl sulfonates (BTS) and FeGA NPs in a certain ratio and encapsulating them in a heat-sensitive hydrogel. FeGA NPs could accelerate the release of Fe2+ under acidic conditions and light, and combine with excess H2O2 in the tumor for chemokinetic treatment. BTS, as a water-soluble prodrug of SO2, can accurately control the release of SO2 gas by virtue of the excellent photothermal conversion ability of FeGA NPs and the acidic pH value of tumor site. SO2 can not only induce cell apoptosis, but also consume excess GSH in cancer cells and increase the content of reactive oxygen species, which seriously destroyed the redox balance in cancer cells and further promotes the therapeutic effect of Fenton reaction. The intelligent FBH system provided a new approach for the synergistic treatment of CDT and SO2 gas, which demonstrated good anticancer effects both in vivo and in vitro.

Abstract Background The purpose of this study was to evaluate and compare the long-term clinical outcomes between the total patellectomy and osteosynthesis with tension band wiring in patients with highly comminuted patella fractures. Methods Between January 1987 and December 2003, this retrospective study included a total of 35 patients (mean age, 51.4±16.8 years) with a minimum of 10 years follow-up period, comprising 29 males and 6 females, who were divided into the total patellectomy group (17 patients) or the open reduction and internal fixation (ORIF) group (18 patients) in the Third Affiliated Hospital of Hebei Medical University. We retrospectively collected patient demographics and data on the type of trauma, fracture type, and postoperative complications. Clinical outcomes including knee range of motion (ROM), 36-Item Short-Form Health Survey (SF-36) score [including physical component score (PCS) and mental component score (MCS)], Knee Injury and Osteoarthritis Outcome Score (KOOS), and Kujala score were evaluated and compared between the two groups. Biodex System dynamometer was used to quantitatively evaluate quadriceps femoris muscle power following measurement of peak torque. Results The mean follow-up periods of the total patellectomy group and the ORIF group were 17.2±5.6 and 16.8±4.9 years, respectively. There were no significant differences between the two groups of patient demographics in terms of the number of patients, age, sex, injury side, time to surgery, type of trauma, and fracture classification (p>0.05). Total patellectomy was comparable to osteosynthesis with tension band wiring in terms of ROM [injured knee: 120.4±3.1° vs 118.6±3.3°; uninjured knee: 126.5±2.8° vs 127.3±1.7°; both p>0.05], peak torque [Injured knee: 96.2±2.3 vs 97.3±2.6, N· m; Uninjured knee: 107.6±2.1 vs 106.3±1.8, N· m; both p>0.05], SF-36 score [PCS: 64.1±18.0 vs 61.5±17.9; MCS: 55.1±13.8 vs 54.3±12.4; both p>0.05], KOOS score [76.3±12.1 vs 73.4±11.7; p>0.05], and Kujala score [67.6±11.8 vs 70.8±11.9; p>0.05] at the final follow-up, while total patellectomy had significantly shorter operation time than ORIF group (47.5±12.1 vs 68.8±22.3, min, p

Abstract Background Acute compartment syndrome (ACS) is an underestimated complication following tibial plateau fractures. Understanding predictors of ACS in the lower leg after a fracture of the tibial plateau may guide earlier diagnosis and promptly decompressed by surgical fasciotomy. To date, however, there are few large-scale sample literatures to investigate the predictors of it. The purpose of our study was to evaluate the prevalence rate of ACS associated with tibial plateau fractures and identified any such predictors with the development of ACS. Materials and methods From January 2015 to January 2020, a total of 1119 consecutive patients (1119 fractures) including 703 males and 416 females with an average age of 40.7 years (18 to 80 years) in tibial plateau fractures who presented to a university-affiliated hospital with level-I trauma center were included. The presence of ACS and associated predictors were collected from patients’ electronic medical records. Associated predictors included gender, age, fracture pattern (open or closed), mechanisms of injury, fracture classification, and underlying disease. Univariate and multivariate logistical regression analyses were performed to identify the predictors of the development of ACS following tibial plateau fractures. Results Of the 1119 fractures of the tibial plateau, 35 (3.1%) developed an acute compartment syndrome. On multivariate analysis, only younger patient age (odds ratio (OR) 2.57; 95% confidence interval (CI), 1.26 to 6.31; P = 0.003), and Schatzker VI type fracture (OR 5.78; 95% confidence interval (CI), 1.78 to 54.34; P = 0.021) were significantly associated with the development of ACS. Other variables did not reach statistical significance. Conclusion Younger patient age and Schatzker VI type fracture were predictors of ACS of the lower leg in adults following tibial plateau fractures. Further studies in the prospective study are still needed to identify the potential risk factors associated with ACS in tibial plateau fractures.

Abstract Background Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy. Methods and results A novel nanocomposite, composed of folic acid (FA) modified mesoporous silica–coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice. Conclusion All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.

Abstract Background The preoperative prevalence of deep venous thromboembolism (DVT) of patella fracture is not well established. The study aimed to investigate the preoperative prevalence, the associated risk factors, and the locations of deep venous thrombosis (DVT) in patients with closed patella fracture. Methods Patients who sustained closed patella fracture between January 1, 2016, and April 1, 2019, were included. Blood analyses and ultrasonography of bilateral lower extremities were routinely performed. Data of demographics, comorbidities, mechanism of injury, fracture type, total hospital stay, time from injury to DVT, and laboratory indexes were prospectively collected and compared between groups with and with non-DVT. Multivariate logistic regression analyses were performed to determine the independent risk factors of DVT. Results Among the study cohort of 790 patients, 35 cases occurred in preoperative DVTs, indicating a prevalence of 4.4%, with 3.2% distal and 1.2% proximal DVT. Age ≥ 65 years old (OR, 3.0, 95% CI, 1.1–8.1), D-dimer > 0.5 mg/L (OR, 2.3, 95% CI, 1.1–4.8), and albumin < 35 g/L (OR, 2.5, 95% CI, 1.2–5.3) were identified to be risk factors of DVT in closed patella fracture. Among the DVTs, 30 cases (85.7%) occurred in the injured extremity, 3 cases (8.6%) in bilateral extremities, and 2 cases (5.7%) solely in the uninjured extremity. Conclusion The prevalence of preoperative DVT in closed patella fracture was 4.4%, with 3.2% for distal and 1.2% for proximal DVT. We recommend individualized risk stratification and early anticoagulation for patients with risk factors (age ≥ 65 years, D-dimer > 0.5 mg/L and albumin < 35g/L).

Abstract Background Lateral tibial plateau fractures (TPFs) are often treated with conventional open reduction and internal fixation (ORIF) through standard anterolateral sub-meniscal arthrotomy. There has been increasing support for “bidirectional rapid redactor” device-assisted closed reduction and internal fixation (CRIF) for treating TPFs. The aim of the present study is to compare the clinical and radiological outcomes between CRIF and ORIF procedures. Methods We performed a retrospective cohort study of 55 lateral TPF patients (Schatzker types I–III) who accepted surgical treatment at our trauma level 1 center between January 2016 and January 2018. They were divided into the CRIF group (32 patients) and the ORIF group (23 patients) based upon the different surgical protocols. The patients’ clinical outcome analysis was evaluated by using the Knee Society Score (KSS) and Rasmussen’s clinical score. For radiological assessment, changes in tibial plateau width (TPW), articular depression depth (ADD), medial proximal tibial angle (MPTA), and posterior tibial slope angle (PTSA) were evaluated using radiographs and computed tomography (CT) scan. Results The CRIF group had a mean follow-up of 28.9 months, and the ORIF group had a mean follow-up of 30.7 months (p>0.05). Furthermore, there was no statistically significant difference in terms of age, gender, injury mechanism, follow-up time, time interval from injury to surgery, and Schatzker classification in the two groups. With respect to the clinical outcomes including the KSS score and Rasmussen’s clinical score, there was also no significant difference (p>0.05). Nevertheless, the CRIF group had lower intra-operative blood loss, shorter hospitalization days, and better range of movement of the knee joint than the ORIF group (p0.05). Conclusion The present study showed that CRIF could achieve comparable clinical outcomes and better radiological results for treating lateral TPFs as compared with conventional ORIF.

Abstract Background Despite tibial plateau fractures are often associated with meniscal tears, the association between meniscal tears and Schatzker classification remains unclear. The purpose of this study was to assess the frequency and patterns of meniscal tears in operatively treated tibial plateau fractures following immediate arthroscopic evaluation after internal fixation of tibial plateau fractures and to reveal the association between these concomitant meniscal tears and Schatzker classification. Methods A total of 252 consecutive patients (166 males and 86 females, mean age 46.7 (19–80) years) with operatively treated tibial plateau fractures admitted to our hospital from January 2016 to May 2019 were performed. Arthroscopic examination for frequency and patterns of meniscal tears was evaluated and documented at the time of surgery, and the association between the frequency and patterns of meniscal tears with Schatzker classification was then analyzed. Results The overall frequency of meniscal tears in TPFs was 67% (168 of 252) with 33% (84 of 252) of these being lateral meniscal tears, and 10% (26 of 252) medial meniscal tears, while 23% (58 of 252) had bilateral meniscal tears. Schatzker II was most commonly associated with meniscal tears, occurring in 72% (71 of 99) of our series. There is no significant difference between the frequency of meniscal tears and Schatzker classification (p > 0.05). The most common patterns of meniscal tears were longitudinal tears in 23% of tibial plateau fractures (59 of 252), and it occurred at a significantly higher frequency in Schatzker II with 43% (43 of 99). Schatzker IV had significantly higher prevalence of bucket-handle tears than other fracture patterns (p < 0.05), and Schatzker VI fractures had significantly higher prevalence of complex tears than other fracture patterns (p < 0.05). For other Schatzker classification, the patterns of meniscal tears demonstrated no statistical difference (p > 0.05). Conclusion The results identified that meniscal tears are commonly seen in each Schatzker classification. Although various patterns of meniscal tears occurred in tibial plateau fractures, the most common patterns were longitudinal tears. Importantly, we suggest that the status of meniscal tears associated with TPFs should be considered at the time of surgery in addition to fracture fixation.

Abstract Background Limited information exists on the incidence of postoperative deep venous thromboembolism (DVT) in patients with isolated patella fractures. The objective of this study was to investigate the postoperative incidence and locations of deep venous thrombosis (DVT) of the lower extremity in patients who underwent isolated patella fractures and identify the associated risk factors. Methods Medical data of 716 hospitalized patients was collected. The patients had acute isolated patella fractures and were admitted at the 3rd Hospital of Hebei Medical University between January 1, 2016, and February 31, 2019. All patients met the inclusion criteria. Medical data was collected using the inpatient record system, which included the patient demographics, patient’s bad hobbies, comorbidities, past medical history, fracture and surgery-related factors, hematological biomarkers, total hospital stay, and preoperative stay. Doppler examination was conducted for the diagnosis of DVT. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors. Results Among the 716 patients, DVT was confirmed in 29 cases, indicating an incidence of 4.1%. DVT involved bilateral limbs (injured and uninjured) in one patient (3.4%). DVT involved superficial femoral common vein in 1 case (3.4%), popliteal vein in 6 cases (20.7%), posterior tibial vein in 11 cases (37.9%), and peroneal vein in 11 cases (37.9%). The median of the interval between surgery and diagnosis of DVT was 4.0 days (range, 1.0-8.0 days). Six variables were identified to be independent risk factors for DVT which included age category (> 65 years old), OR, 4.44 (1.34-14.71); arrhythmia, OR, 4.41 (1.20-16.15); intra-operative blood loss, OR, 1.01 (1.00-1.02); preoperative stay (delay of each day), OR, 1.43 (1.15-1.78); surgical duration, OR, 1.04 (1.03-1.06); LDL-C (> 3.37 mmol/L), OR, 2.98 (1.14-7.76). Conclusion Incidence of postoperative DVT in patients with isolated patella fractures is substantial. More attentions should be paid on postoperative DVT prophylaxis in patients with isolated patella fractures. Identification of associated risk factors can help clinicians recognize the risk population, assess the risk of DVT, and develop personalized prophylaxis strategies.

Prediction of Chlorophyll-a (Chl-a) concentration is significant for marine ecology and environmental protection. This paper presents an integrated approach to forecast seasonal Chl-a concentration in coastal waters. Before modeling, feature construction procedures, such as simplification, combination, and normalization, are conducted to identify the potentially significant features. The feature extraction method based on Random Forest (RF) and eXtreme Gradient BOOSTing (XGBoost) is applied to select relevant variables. Then, we propose a Cluster-stacking-based approach which includes a station-oriented clustering model and a stacking-based regression model. The former model is used to divide the observation stations into several groups, thus partitions the study region into several sub-regions and the study dataset into several subsets according to the corresponding stations. In each subset, single regression models including K-Nearest Neighbor (KNN), Support Vector Regression (SVR), Multi-Layer Perceptron regression (MLP) and XGBoost are established in level 0 space and integrated by RF in level 1 space via stacked generalization. We compare the performance of the Cluster-stacking model with that of Cluster-KNN, Cluster-SVR, Cluster-MLP, Cluster-XGBoost and the regression stacking model without cluster. The model evaluation shows that the Cluster-stacking-based approach outperforms others in forecasting Chl-a concentration with a coefficient of determination (R2) of 0.848 and a mean absolute error (MAE) of 0.665 ug/l.

Abstract Patients with osteosarcoma exhibiting resistance to chemotherapy or presenting with metastasis usually have a poor prognosis. Osteosarcoma stem cells (OSCs) are a potential cause of tumor metastasis, relapse, and chemotherapy resistance. Therefore, it is necessary to develop novel therapeutic drugs, which not only kill osteosarcoma cells but also target OSCs. This study aims to explore the anti‐osteosarcoma effects of Bruceine D (BD), a natural compound derived from Brucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere‐forming and self‐renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD showed significant anti‐osteosarcoma activity without obvious side effects in vivo. Collectively, the results of this study demonstrated that BD exerts a strong inhibitory effect on tumor growth and stem cell like traits of osteosarcoma which may be partially due to STAT3 inhibition, suggesting that BD maybe a promising therapeutic candidate against osteosarcoma.

Increasing evidence suggests that an exogenous electromagnetic field might be involved in many biologic processes which are of great importance for therapeutic interventions. Pulsed electromagnetic fields (PEMFs) are known to be a noninvasive, safe and effective therapy agent without apparent side effects. Numerous studies have shown that PEMFs possess the potential to become a stand-alone or adjunctive treatment modality for treating musculoskeletal disorders. However, several issues remain unresolved. Prior to their widely clinical application, further researches from well-designed, high-quality studies are still required to standardize the treatment parameters and derive the optimal protocol for health-care decision making. In this review, we aim to provide current evidence on the mechanism of action, clinical applications, and controversies of PEMFs in musculoskeletal disorders.

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration.

A novel fluorescent reagent for determination of ammonium, 4-methoxyphthalaldehyde (MOPA), was successfully synthesized in this study. Under alkaline conditions, MOPA could reacted with ammonium rapidly at room temperature, producing fluorescent substance which had maximum excitation at 370 nm and emission wavelength at 454 nm. Based on this, a novel fluorescence analysis method was established for the determination of trace ammonium in natural water. Experimental parameters including reagent concentration, pH, reaction equilibrium time, and metal ions masking agent were optimized. The results showed that the optimized MOPA concentration was 0.12 g/L, pH was in the range of 11.2–12.0, and sulfite concentration was 0.051 g/L, respectively. Metal ions masking agent had no obvious effect on the fluorescence signal. With the reaction time of 15 minutes, linear range of this method was between 0.025 and 0.300 μmol/L, and the method detecting limit was 0.0058 μmol/L. The matrix recovery of the proposed method was in the range of 93.6–108.1%. Compared with the OPA method, this method was much more sensitive and rapid without the interference of background peak and would be more suitable for developing a portable fluorescence detection system.

This paper deals with the modeling of fault for analog circuits. A two-dimensional (2D) fault model is first proposed based on collaborative analysis of supply current and output voltage. This model is a family of circle loci on the complex plane, and it simplifies greatly the algorithms for test point selection and potential fault simulations, which are primary difficulties in fault diagnosis of analog circuits. Furthermore, in order to reduce the difficulty of fault location, an improved fault model in three-dimensional (3D) complex space is proposed, which achieves a far better fault detection ratio (FDR) against measurement error and parametric tolerance. To address the problem of fault masking in both 2D and 3D fault models, this paper proposes an effective design for testability (DFT) method. By adding redundant bypassing-components in the circuit under test (CUT), this method achieves excellent fault isolation ratio (FIR) in ambiguity group isolation. The efficacy of the proposed model and testing method is validated through experimental results provided in this paper.

In the existence of appropriate amount of disodium ethylenediaminetetraacetate (EDTA), precipitation would not occur in seawater and other natural waters even if the sample solution was adjusted to strong basicity, and the NH3-OPA-sulfite reaction at the optimal pH range could be used to determine ammonium in natural waters. Based on this, a modified o-phthalaldehyde fluorometric analytical method has been established to determine ultratrace ammonium in natural waters. Experimental parameters, including reagent concentration, pH, reaction time, and effect of EDTA, were optimized throughout the experiments based on univariate experimental design. The results showed that the optimal pH range was between 10.80 and 11.70. EDTA did not obviously affect the fluorometric intensity. The linearity range of the proposed method was 0.032–0.500 µmol/L, 0.250–3.00 µmol/L, and 1.00–20.0 µmol/L at the excitation/emission slit of 3 nm/5 nm, 3 nm/3 nm, and 1.5 nm/1.5 nm, respectively. The method detection limit was 0.0099 µmol/L. Compared to the classical OPA method, the proposed method had the advantage of being more sensitive and could quantify ultratrace ammonium without enrichment.

Emergency has attracted global attentions of government and the public, and it will easily trigger a series of serious social problems if it is not supervised effectively in the dissemination process. In the Internet world, people communicate with each other and form various virtual communities based on social networks, which lead to a complex and fast information spread pattern of emergency events. This paper collects Internet data based on data acquisition and topic detection technology, analyzes the process of information spread on social networks, describes the diffusions and impacts of that information from the perspective of random graph, and finally seeks the key paths through an improved IBF algorithm. Application cases have shown that this algorithm can search the shortest spread paths efficiently, which may help us to guide and control the information dissemination of emergency events on early warning.