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Abstract Developing high-performance nanomedicines to enhance antitumor efficacy remains a hot point in the field of biomedicine. In this study, we designed a versatile nanocomposite (FeS₂@COF-HA/AIPH) integrating covalent organic frameworks (COF) functionalized with pyrite (FeS₂) for synergistic photothermal (PTT), chemodynamic (CDT), thermodynamic (TDT) therapies, and immunotherapy. The superior photothermal effects and catalytic capabilities of FeS₂@COF enabled a minimally invasive PTT/CDT combination. The nanoplatform, with its mesoporous structure, also served as a drug delivery system, encapsulating the thermos-decomposable initiator AIPH. The hyaluronic acid (HA) coating not only improved tumor-targeting efficiency but also prevented nonspecific AIPH release. Under near-infrared (NIR) irradiation, the localized hyperthermia triggered AIPH decomposition, generating toxic alkyl radicals (•R) for TDT, further enhancing CDT efficiency. The combination of PTT, CDT, TDT, and immunotherapy led to potent antitumor effects with minimal systemic toxicity, both in vitro and in vivo. Notably, the nanoplatform effectively reprogrammed tumor-associated macrophages (TAMs) from an M2 to M1 phenotype, boosting antitumor immunity. This multifunctional platform thus offers a promising strategy for integrated PTT, CDT, TDT, and immune activation in tumor therapy.

Abstract Background Myocardial infarction (MI) is a major disease with high morbidity and mortality worldwide. However, existing treatments are far from satisfactory, making the exploration of potent molecular targets more imperative. The E3 ubiquitin ligase RING finger protein 5 (RNF5) has been previously reported to be involved in several diseases by regulating ubiquitination-mediated protein degradation. Nevertheless, few reports have focused on its function in cardiovascular diseases, including MI. Methods In this study, we established RNF5 knockout mice through precise CRISPR-mediated genome editing and utilized left anterior descending coronary artery ligation in 9-11-week-old male C57BL/6 mice. Subsequently, serum biochemical analysis and histopathological examination of heart tissues were performed. Furthermore, we engineered adenoviruses for modulating RNF5 expression and subjected neonatal rat cardiomyocytes to oxygen-glucose deprivation (OGD) to mimic ischemic conditions, demonstrating the impact of RNF5 manipulation on cellular viability. Gene and protein expression analysis provided insights into the molecular mechanisms. Statistical methods were rigorously employed to assess the significance of experimental findings. Results We found RNF5 was downregulated in infarcted heart tissue of mice and NRCMs subjected to OGD treatment. RNF5 knockout in mice resulted in exacerbated heart dysfunction, more severe inflammatory responses, and increased apoptosis after MI surgery. In vitro, RNF5 knockdown exacerbated the OGD-induced decline in cell activity, increased apoptosis, while RNF5 overexpression had the opposite effect. Mechanistically, it was proven that the kinase cascade initiated by apoptosis signal-regulating kinase 1 (ASK1) activation was closely regulated by RNF5 and mediated RNF5’s protective function during MI. Conclusions We demonstrated the protective effect of RNF5 on myocardial infarction and its function was dependent on inhibiting the activation of ASK1, which adds a new regulatory component to the myocardial infarction associated network and promises to enable new therapeutic strategy.

Abstract Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual‐delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor β (TGF‐β) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Abstract Purpose To analyze return to work and sports, and health-related quality of life (HRQoL) after closing-wedge distal femoral osteotomy (CWDFO) for valgus deformity and lateral compartmental osteoarthritis. Methods Thirty-three patients underwent isolated CWDFO in our center between January 2018 and June 2020 were enrolled, of whom 32 and 23 patients were included in the return-to-work and return-to-sports analyses, respectively. Short Form-36 (SF-36), Tegner score, Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) pain score were compared preoperatively and postoperatively. And postoperative complications were recorded. Results Overall, 33 patients were contacted at a mean follow-up of 37.94 ± 6.68 months, with a median age of 35 years (range: 26–63 years) at the surgery time. The physical component summary of SF-36 (p

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

Abstract Background There is no consensus about intertrochanteric fractures with lateral wall treated with intramedullary nail—proximal femoral nail antirotation (PFNA). The aim of the present study was to compare function outcomes between lateral wall and no lateral wall fractures after surgery by PFNA. Methods This retrospective study evaluated patients with or without lateral wall fractures who underwent PFNA between January 2015 and June 2018. The operative time, intraoperative blood loss, time to fracture healing, complications and functional outcomes qualified by Harris hip score and Parker − Palmer mobility score (PPMS) were compared between the two groups. Results Two groups were comparable with regard to patient age, sexual distribution, mechanism of injury, fracture type, body mass index (BMI), Time to surgery, American Society of Anesthesiologists (ASA) score and quality of reduction. The incomplete group had a longer operation time (54.1 ± 8.74 min vs. 51.0 ± 9.86 min) and more intraoperative blood loss (228.4 ± 48.8 ml vs. 151.3 ± 43.5 ml) in comparison with the control group (P 0.05), respectively. Similar results were obtained about PPMS. We found no difference in Weight bearing time, Time of fracture healing, and Complications between incomplete group and intact group. Conclusions There is no substantial difference in functional results or complication rates for intertrochanteric fractures with lateral wall fractures, except from increased blood loss and operation time. We believe that an intramedullary nail will be sufficient to repair an intertrochanteric fracture with or without a lateral wall fracture.

Aims: This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. Methods: A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data. Results: After the screening, 44 studies were included with 1,079 patients and 1,083 segments of infected bone defects treated with the induced membrane technique. The mean defect size was 6.8 cm (0.5 to 30). After the index second stage procedure, 85% (797/942) of segments achieved union, and 92% (999/1,083) of segments achieved final healing. The multivariate analysis with data from 296 patients suggested that older age was associated with higher nonunion risk. Patients with external fixation in the second stage had a significantly higher risk of developing nonunion, increasing the need for additional procedures. The autografts harvested from the femur reamer-irrigator-aspirator increased nonunion, infection recurrence, and additional procedure rates. Conclusion: The induced membrane technique is an effective technique for treating infected bone defects. Internal fixation during the second stage might effectively promote bone healing and reduce additional procedures without increasing infection recurrence. Future studies should standardize individual patient data prospectively to facilitate research on the affected patient outcomes. Cite this article: Bone Joint Res 2023;12(9):546–558.

Background Patients with colorectal cancer often have anemia and other symptoms after diagnosis, especially in patients with advanced colorectal cancer. This study explored the association between different types of preoperative anemia and tumor characteristics and inflammatory response in patients with colorectal cancer and to evaluate the prognosis of patients with different types of anemia before operation. Methods The clinical data of 95 patients with colorectal cancer treated in the Fourth Hospital of Hebei Medical University from February 2016 to January 2018 were retrospectively analyzed. According to the hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean hemoglobin content (MCH) and mean hemoglobin concentration (MCHC), the patients were divided into the non-anemia group, normal cell anemia group, and small cell anemia group. The three groups’ general data, oncological characteristics, and mGPS scores were compared. The patients were followed up for five years, and the survival analysis was carried out. The cox proportional hazard regression model was used to analyze the prognostic factors of patients with colorectal cancer. Results The preoperative anemia rate of patients with colorectal cancer was 43.15% (41/95). There were significant differences in gender, weight loss, CA724, tumor location, tumor size, TNM stage, mGPS score, and positive expression rate of Ki-67 among different anemia groups. There was a significant difference in survival time among a non-anemia group, small cell anemia group, and normal cell anemia group (P

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood.Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein.Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU.Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.

Osteosarcoma, occurring most frequently in adolescents, are highly malignant bone tumor and prone to develop local recurrence and long-distance metastasis. Therefore, new comprehensive therapeutic strategies for osteosarcoma are urgently needed. Different from traditional photothermal therapy (PTT), low temperature PTT (LTPTT) not only brings less heat damages to the surrounding normal tissues but also prevent tumor metastasis. Nevertheless, its therapeutic effects are severely attenuated due to the tumor thermo-resistance induced by the overexpression of heat shock protein (HSP). In our work, an acid-responsive core–shell nanocomposite was fabricated for cancer therapy. The nanoplatform can independently encapsulate alkyl radical initiator 2,2-azobis[2-(2-imidazolin-2-yl) propane]-dihydroch-loride (AIPH) in the mesoporous polydopamine (MPDA) core and HSP inhibitor (gambogic acid, GA) in the zeolite imidazolate framework-8 (ZIF-8) microporous shell, called MPDA/AIPH@ZIF-8/GA (MAZG), which could achieve the combined functions of LTPTT and thermodynamic therapy (TDT). After endocytosing by tumor cells, the pH-responsive degradation of the ZIF-8 coating stimulates the rapid release of GA, which can effectively inhibit HSP expression in advance, and then simultaneously enhanced the therapeutic efficacy of LTPTT. Further, both in vitro and in vivo experiments have demonstrated that the as-synthesized MAZG nanocomposite exhibited favorable biosafety and remarkable tumor growth inhibition.

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.

This study aimed to evaluate the efficiency and safety of tranexamic acid for blood management during high tibial osteotomy (HTO). A systematic search was conducted in Medline, Embase, and the Cochrane library database. Six studies and 208 patients were included in this meta‐analysis using Review Manager V.5.3 and Stata 15.1 software. For primary outcomes, tranexamic acid lowered the total blood loss (WMD = –219.47, 95% CI [−355.61, −83.33], P = 0.002). For secondary outcomes, a significant reduction was found for decreased hemoglobin (POD1: WMD = –9.86, 95% CI [−13.45, −6.28], P 40%: WMD = –53.11, 95% CI [−100.16, −6.05], P = 0.03; 40% ≥ M/F ≥ 20%: WMD = –362.20, 95% CI [−423.96, −300.45], P 40%: WMD = –7.11, 95% CI [−10.75, −3.47], P

The process of bone regeneration involves the interaction of the skeletal, blood, and immune systems. Bone provides a solid barrier for the origin and development of immune cells in the bone marrow. At the same time, immune cells secrete related factors to feedback on the remodeling of the skeletal system. Pathological or traumatic injury of bone tissue involves changes in blood supply, cell behavior, and cytokine expression. Immune cells and their factors play an essential role in repairing foreign bodies in bone injury or implantation of biomaterials, the clearance of dead cells, and the regeneration of bone tissue. This article reviews the bone regeneration application of the bone tissue repair microenvironment in bone cells and immune cells in the bone marrow and the interaction of materials and immune cells.

Abstract Background Colorectal cancer (CRC) is major cancer-related death. The aim of this study was to identify differentially expressed and differentially methylated genes, contributing to explore the molecular mechanism of CRC. Methods Firstly, the data of gene transcriptome and genome-wide DNA methylation expression were downloaded from the Gene Expression Omnibus database. Secondly, functional analysis of differentially expressed and differentially methylated genes was performed, followed by protein-protein interaction (PPI) analysis. Thirdly, the Cancer Genome Atlas (TCGA) dataset and in vitro experiment was used to validate the expression of selected differentially expressed and differentially methylated genes. Finally, diagnosis and prognosis analysis of selected differentially expressed and differentially methylated genes was performed. Results Up to 1958 differentially expressed (1025 up-regulated and 993 down-regulated) genes and 858 differentially methylated (800 hypermethylated and 58 hypomethylated) genes were identified. Interestingly, some genes, such as GFRA2 and MDFI, were differentially expressed-methylated genes. Purine metabolism (involved IMPDH1), cell adhesion molecules and PI3K-Akt signaling pathway were significantly enriched signaling pathways. GFRA2, FOXQ1, CDH3, CLDN1, SCGN, BEST4, CXCL12, CA7, SHMT2, TRIP13, MDFI and IMPDH1 had a diagnostic value for CRC. In addition, BEST4, SHMT2 and TRIP13 were significantly associated with patients’ survival. Conclusions The identified altered genes may be involved in tumorigenesis of CRC. In addition, BEST4, SHMT2 and TRIP13 may be considered as diagnosis and prognostic biomarkers for CRC patients.

Purpose: In recent years, immune checkpoint inhibitors have become a major therapeutic method for the treatment of metastatic colorectal cancer (mCRC). Growing evidence indicates that tumour-infiltrating lymphocytes (TILs) in the tumour microenvironment are a prerequisite for the effectiveness of PD-1/PD-L1 blockade therapy. In this study, we aimed to compare PD-L1 expression and cluster of differentiation 4 (CD4) and CD8 TIL infiltration in primary tumours and paired metastases. Patients and methods: Altogether, 111 patients with mCRC who underwent surgery at our hospital were included. PD-L1, CD4, and CD8 expression were detected by immunohistochemistry in a tissue microarray. PD-L1 expression was assessed using the combined positivity score (CPS), and a score ≥1 was judged as positive. The area proportion of TILs with positive staining ≥10% was classified as “high”, while

BackgroundFemoral neck fracture is a common fracture in orthopedic practice. This study aimed to compare the clinical outcomes between the femoral neck system and dynamic hip system blade for the treatment of femoral neck fracture in young patients.MethodsThis retrospective study included 43 and 52 patients who underwent treatment for femoral neck fracture with the femoral neck system and dynamic hip system blade, respectively, between August 2019 and August 2020. Operative indexes, including operation duration, blood loss, incision length, postoperative complications (femoral neck shortening, non-union, screw pull-out, femoral head necrosis), and Harris scale scores were recorded and analyzed.ResultsCompared to that with the dynamic hip system blade, the femoral neck system showed significantly less operation duration (femoral neck system vs. dynamic hip system blade: 47.09 ± 9.19 vs. 52.90 ± 9.64, P = 0.004), less blood loss (48.53 ± 10.69 vs. 65.31 ± 17.91, P

Although photothermal therapy (PTT) have aroused substantial attention in the treatment of various types of tumors, the antitumor therapeutic efficacy is still unsatisfactory when using PTT alone. Very recently, oxygen-independent free-radical generation based on thermodynamic therapy (TDT) has emerged as a potential powerful therapeutic strategy for hypoxic cancer therapy. Herein, in this work, an intelligent hypoxia-independent free radical nanogenerator (CuS/AIPH@MnO2, denoted as CAM) was fabricated by in situ coating manganese dioxide (MnO2) shell onto the surface of as 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH)-loaded mesoporous hollow mesoporous copper sulfide (CuS). The local hyperthermal generated by CAM upon NIR laser irradiation not only permitted PTT, but also promoted the disintegration of AIPH for generation of oxygen-independent free radicals, exerting the advantages of combination therapy of PTT/TDT for effective tumor ablation. Simultaneously, both in vitro and in vivo results have demonstrated the synergistic therapeutic efficacy of PTT/TDT for remarkable tumor growth inhibition. In addition, the favorable biocompatibility and low cytotoxicity of the as-synthesized nanoparticles were verified both in vitro and in vivo. Collectively, this work proposed an attractive and promising strategy in cancer therapy based on generation of oxygen-irrelevant toxic free radicals, which exhibits great potential for clinical translations in hypoxic tumor therapy.

Abstract Background The use of a tourniquet during high tibial osteotomy (HTO) is a routine procedure, but there is currently no research on the benefits and potential risks of tourniquet use during HTO. The aim of this study was to investigate the impact of tourniquet on perioperative blood loss, early functional recovery and complications in opening wedge HTO with modern tranexamic acid protocols. Methods This was a retrospective cohort study of patients who underwent unilateral opening wedge HTO between January 2019 and September 2020. All patients were divided into two groups according to whether a tourniquet was applied during HTO. Patients in both groups received the same surgical procedures, tranexamic acid protocols and other perioperative treatments. Preoperative baseline data, intraoperative data, early postoperative recovery and all complications during the 3-month follow-up were collected and compared between the two groups. Results A total of 62 patients were enrolled in this study, including 32 in the tourniquet group and 30 in the non-tourniquet group. There was no significant difference in preoperative baseline data between the two groups (P > 0.05 in all). Intraoperative blood loss in the tourniquet group was significantly lower than that in the non-tourniquet group (80.22 ml versus 94.00 ml, P < 0.001), but there was no difference in total blood loss (187.39 ml versus 193.31 ml, P = 0.714). And no patient in either group required blood transfusion. In terms of early postoperative recovery, tourniquet use significantly increased pain scores and reduced knee range of motion on the first and second postoperative days, but there was no significant difference between the two groups at postoperative third day and third month. Furthermore, there was no significant difference between the two groups in terms of lower limb force line correction, length of stay, Knee Society Score or the incidence of complications during the 3-month follow-up (P > 0.05 in all). Conclusions In opening wedge HTO with modern tranexamic acid protocols, not using a tourniquet does not increase perioperative total blood loss or the risk of complications, but facilitates early postoperative recovery by reducing pain and increasing range of motion.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. Results We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. Conclusion Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects. Graphical abstract

The symbiotic relationship between beneficial microorganisms and plants plays a vital role in natural and agricultural ecosystems. Although Peucedanum praeruptorum Dunn is widely distributed, its development is greatly limited by early bolting. The reason for early bolting in P. praeruptorum remains poorly characterized. We focus on the plant related microorganisms, including endophytes and rhizosphere microorganisms, by combining the traditional isolation and culture method with metagenomic sequencing technology. We found that the OTUs of endophytes and rhizosphere microorganisms showed a positive correlation in the whole growth stage of P. praeruptorum. Meanwhile, the community diversity of endophytic and rhizosphere fungi showed an opposite change trend, and bacteria showed a similar change trend. Besides, the microbial communities differed during the pre- and post-bolting stages of P. praeruptorum. Beneficial bacterial taxa, such as Pseudomonas and Burkholderia, and fungal taxa, such as Didymella and Fusarium, were abundant in the roots in the pre-bolting stage. Further, a strain belonging to Didymella was obtained by traditional culture and was found to contain praeruptorin A, praeruptorin B, praeruptorin E. In addition, we showed that the fungus could affect its effective components when it was inoculated into P. praeruptorum. This work provided a research reference for the similar biological characteristics of perennial one-time flowering plants, such as Saposhnikovia divaricate, Angelica sinensis and Angelica dahurica.

Abstract Background The femoral neck system (FNS) may be a valid alternative for treating femoral neck fractures, but few studies have compared the outcomes between FNS and cannulated cancellous screws. This study aimed to compare the clinical efficacy and complications of FNS with those of inverted cannulated cancellous screws (ICCS) for the treatment of femoral neck fractures in adults. Methods This retrospective study evaluated patients with femoral neck fractures who underwent FNS or ICCS internal fixation between June 2019 and January 2020. The operative time, intraoperative blood loss, number of fluoroscopies, length of surgical incision, length of hospital stay, time to fracture healing, and other indicators were compared between the two groups. The incidence of complications such as nonunion, avascular necrosis of the femoral head, loosening of the internal fixation, and shortening of the femoral neck during follow-up was also assessed in both groups. Results Among the 92 patients included, 47 and 45 patients were categorized into the FNS and ICCS groups, respectively. Follow-up ranged from 14 to 24 months. There were no significant between-group differences in sex, age, side of the injured limb, and type of fracture and in operative time, intraoperative blood loss, incision length, and length of hospital stay (all P > 0.05). The incidence of complications such as fracture nonunion, avascular necrosis of the femoral head, and screw loosening was also comparable between the two groups. However, the number of fluoroscopies was significantly lower in the FNS group than in the ICCS group (P < 0.05). The fracture healing time was also significantly lower in the FNS group than in the ICCS group (P < 0.05). Furthermore, the femoral neck shortening and Harris hip score at the last follow-up were significantly better in the FNS group than in the ICCS group (P < 0.05). Conclusions FNS for femoral neck fractures improves hip functional recovery and reduces the femoral neck shortening rate and fluoroscopy exposure postoperatively. Thus, FNS can be an alternative to ICCS for the treatment of femoral neck fractures.

Abstract Background Venous thromboembolism (VTE) is a common complication of hospitalized trauma patients and has an adverse impact on patient outcomes. However, there is still a lack of appropriate tools for effectively predicting VTE for trauma patients. We try to verify the accuracy of the Caprini score for predicting VTE in trauma patients, and further improve the prediction through machine learning algorithms. Methods We retrospectively reviewed emergency trauma patients who were admitted to a trauma center in a tertiary hospital from September 2019 to March 2020. The data in the patient’s electronic health record (EHR) and the Caprini score were extracted, combined with multiple feature screening methods and the random forest (RF) algorithm to constructs the VTE prediction model, and compares the prediction performance of (1) using only Caprini score; (2) using EHR data to build a machine learning model; (3) using EHR data and Caprini score to build a machine learning model. True Positive Rate (TPR), False Positive Rate (FPR), Area Under Curve (AUC), accuracy, and precision were reported. Results The Caprini score shows a good VTE prediction effect on the trauma hospitalized population when the cut-off point is 11 (TPR = 0.667, FPR = 0.227, AUC = 0.773), The best prediction model is LASSO+RF model combined with Caprini Score and other five features extracted from EHR data (TPR = 0.757, FPR = 0.290, AUC = 0.799). Conclusion The Caprini score has good VTE prediction performance in trauma patients, and the use of machine learning methods can further improve the prediction performance.

Arisaema bockii Engler is a perennial herbaceous medicinal plant, which is widely distributed in many provinces in China such as Anhui, Jiangsu, and Zhejiang. In this study, the complete chloroplast genome sequence of A. bockii was assembled and characterized based on high-throughput sequencing data. The total length of chloroplast genome was 175,537 bp, including large single-copy (LSC) and small single-copy (SSC) regions of 98,870 bp and 23,345 bp, respectively, which were separated by a pair of 27,161 bp inverted repeat (IR) regions. The genome contained 129 genes, including 84 protein-coding genes, 36 tRNA genes, 8 rRNA genes, and one pseudogene. The overall GC content of the genome was 33.6%. A phylogenetic tree reconstructed by 30 chloroplast genomes revealed that A. bockii was mostly related to the same genus species A. ringens, A. franchetianum and A. erubescens. The work reported the first complete chloroplast genome of A. bockii, which may provide some useful information to the evolution of the family Araceae.

Radiotherapy (RT) is a frequently used means in clinical tumor treatment. The outcome of RT varies, however, to a great extent, due to RT resistance or intolerable dose, which might be resolved by the development of radio-sensitizing strategies. Here, we report redox-sensitive iodinated polymersomes (RIP) carrying histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA, vorinostat), as a new dual-functional nano-radiosensitizer for breast cancer radiotherapy. SAHA-loaded RIP (RIP-SAHA) with a size of about 101 nm exhibited good colloidal stability while the reduction-activated release of SAHA, giving rise to better antitumor effect to 4T1 breast carcinoma cells than free SAHA. Accordingly, RIP-SAHA combined with a 4 Gy dose of X-ray radiation led to significantly enhanced suppression of 4T1 cells compared with SAHA combined 4 Gy of X-ray radiation, as a result of enhanced DNA damage and impeded DNA damage repair. The pharmacokinetics and biodistribution studies by single-photon emission computed tomography (SPECT) with 125I-labeled SAHA (125I-SAHA) showed a 17.3-fold longer circulation and 237.7-fold better tumor accumulation of RIP-SAHA over SAHA. The systemic administration of RIP-SAHA greatly sensitized radiotherapy of subcutaneous 4T1 breast tumors and brought about significant inhibition of tumor growth, without causing damages to major organs, compared with radiotherapy alone. RIP not only enhanced SAHA delivery but also acted as a radiosensitizer. RIP-SAHA emerges as a smart dual-functional nano-radiosensitizer to effectively enhance tumor radiotherapy.

Peucedanum praeruptorum Dunn is a commonly used traditional Chinese medicine that is abundant in furano- and dihydropyrano coumarins. When P. praeruptorum reaches the bolting stage, the roots gradually lignified, and the content of coumarins declines rapidly. Non-bolting has always been a decisive factor for harvesting the P. praeruptorum materials. To evaluate the amount of coumarin components in unbolted and bolted P. praeruptorum, the variations of praeruptorin A, praeruptorin B, praeruptorin E, peucedanocoumarin I, and peucedanocoumarin II were determined. Additionally, 336,505 transcripts were obtained from the comparative transcriptome data. Among them, a total of 1,573 differentially expressed genes were screened out. To identify the critical genes involved in coumarin biosynthesis, comparative transcriptomics coupled with co-expression associated analysis was conducted. Finally, coumarin biosynthesis-related eighteen candidate genes were selected for the validation of qPCR. Additionally, a phylogenetic tree and the expression profile of ATP-binding cassette (ABC) transporters were constructed. To clarify the main genes in the regulation of coumarin biosynthesis, the interaction network of the co-expression genes from thirteen modules was constructed. Current results exhibited the significant increment of praeruptorin A, praeruptorin B and praeruptorin E in the bolted P. praeruptorum. Although, peucedanocoumarin I and peucedanocoumarin II were slightly increased. Besides the content of coumarins, the essential genes involved in the coumarin biosynthesis also exhibited an overall downward trend after bolting. Three peroxidases (PRXs) involved in the production of lignin monomers had been demonstrated to be downregulated. PAL, C4H, HCT, COMT, CCoAOMT, and some ABC transporters were dramatically downregulated at the bolting stage. These results indicated that the downregulation of coumarin biosynthetic genes in the bolted P. praeruptorum ultimately reduced the formation of coumarins. However, the mechanism through which bolting indirectly affects the formation of coumarin still needs extra functional verification.

With the deepening of drilling depth, the difficulty of drilling engineering increases gradually due to the complex geological conditions. The traditional mechanical drilling method shows the problems of high energy consumption, low efficiency, long cycle and high cost. Because of the characteristics of rock, the high abrasiveness of rock causes great wear to the bit, which becomes an important factor affecting the drilling rate. High voltage electric pulse (Abbreviated as HVEP later in this paper) drilling technology is a new technology developed in the past several decades. The technology uses plasma channel, water jet or shock wave generated by high voltage electric pulse discharge to break rock. It has the characteristics of environmental protection, directional breaking, easy control of rock breaking process and fast speed in the face of complex hard rock. In this paper, the mechanism and technology of rock breaking by high voltage electric pulse method in deep drilling are studied, and the functional test is carried out.

Abstract Background Articular cartilage lesions generated by trauma or osteoarthritis are the most common causes of pain and disability in patients. Abstract The development of photopolymerizable hydrogels has allowed for significant advances in cartilage repair procedures. Such three-dimensional (3D) networks of polymers that carry large amounts of water can be created to resemble the physical characteristics of the articular cartilage and be delivered into ill-defined cartilage defects as a liquid solution prior to polymerization in vivo for perfect fit with the surrounding native tissue. These hydrogels offer an adapted environment to encapsulate and propagate regenerative cells in 3D cultures for cartilage repair. Among them, mesenchymal stem cells and chondrocytes may represent the most adapted sources for implantation. They also represent platforms to deliver therapeutic, biologically active factors that promote 3D cell differentiation and maintenance for in vivo repair. Conclusion This review presents the benefits of photopolymerization of hydrogels and describes the photoinitiators and materials in current use for enhanced cartilage repair.

Abstract Background The supercapsular percutaneously-assisted total hip arthroplasty (SuperPath) was proposed to be minimally invasive and tissue sparing with possible superior postoperative outcomes to traditional approaches of total hip arthroplasty (THA). Here, we compared the short-term outcomes of staged THA with the SuperPath or through posterolateral approach (PLA) for bilateral osteonecrosis of the femoral head (ONFH). Methods Patients with bilateral late-stage ONFH were prospectively recruited from our department from March 2017 to March 2018. Staged bilateral THAs with one side SuperPath and the other side PLA were performed consecutively in the same patients with right and left hips alternating within approaches. The average time interval between the staged THAs was 3 months. Perioperative status (operation time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay) and postoperative function (range of motion, pain, and hip function) were recorded and compared between the SuperPath and PLA approaches within 12-month postoperatively. Results Four male patients (age, 51.00 ± 4.54; BMI, 21.49 ± 1.73) with bilateral alcohol-induced ONFH (Ficat III/IV) were followed up over 12 months postoperatively. Compared with the PLA, the SuperPath yielded shorter incision length (7.62 vs. 11.12 cm), longer operation time (103.25 vs. 66.50 min), more blood loss (1108.50 vs. 843.50 ml), deficient abduction angle of the acetabular cup (38.75° vs. 44.50°), and inferior early-term hip function (Harris hip score, 72.50 vs. 83.25) at 12-month postoperatively. Soft tissue damage, length of hospital stay, postoperative pain, postoperative range of motion, and 12-month patient satisfaction were comparable between both approaches. Conclusion The SuperPath may be a minimally invasive technique but the present study shows less favorable short-term outcomes than PLA for total hip arthroplasty in osteonecrosis of the femoral head. More investigations are required to provide convincing favorable evidences of the SuperPath over other traditional THA approaches. Trial registration information The trial was retrospectively registered in https://www.researchregistry.com (No. Researchregistry4993) on July 04, 2019. The first participant was enrolled on March 13, 2017.

Metallic ions have been widely investigated and incorporated into bone substitutes for bone regeneration owing to their superior capacity to induce angiogenesis and osteogenesis. Exosomes are key paracrine mediators that play a crucial role in cell-to-cell communication. However, the role of exosomes in metallic ion-induced bone formation and their underlying mechanisms remain unclear. Thus, this review systematically analyzes the effects of metallic ions and metallic ion-incorporated biomaterials on exosome secretion from mesenchymal stem cells (MSCs) and macrophages, as well as the effects of secreted exosomes on inflammation, angiogenesis, and osteogenesis. In addition, possible signaling pathways involved in metallic ion-mediated exosomes, followed by bone regeneration, are discussed. Despite limited investigation, metallic ions have been confirmed to regulate exosome production and function, affecting immune response, angiogenesis, and osteogenesis. Although the underlying mechanism is not yet clear, these insights enrich our understanding of the mechanisms of the metallic ion-induced microenvironment for bone regeneration, benefiting the design of metallic ion-incorporated implants.

Abstract Background Tibia infected nonunion and chronic osteomyelitis are challenging clinical presentations. Bone transportation with external or hybrid fixators (combined external and internal fixators) is versatile to solve these problems. However, the infection-free rates of these fixator systems are unknown. Additionally, the prognosis factors for results of bone transportation are obscure. Therefore, this systematic review and meta-analysis was conducted to answer these questions. Methods A systematic review was conducted following the PRISMA-IPD guidelines. Relevant publications from January 1995 to September 2018 were compiled from Medline, Embase, and Cochrane. The infection-free rates of external and hybrid fixators were achieved by synthesizing aggregate data and individual participant data (IPD). IPD was analyzed by two-stage method with logistical regression to identify prognosis factors of sequelae. Results Twenty-two studies with 518 patients were identified, including 11 studies with 167 patients’ IPD, and 11 studies with 351 patients’ aggregate data. The infection-free rate of hybrid fixator group was 86% (95%CI: 79–94%), lower than that of external fixator which was 97% (95%CI: 95–98%,). The number of previous surgeries was found predict factor of bone union sequelae (p = 0.04) and function sequelae(p

Mechanical equipment in the field of aerospace that is used only once is called disposable machinery. As a piece of typical disposable machinery, disposable harmonic gear exhibit stiffness failure with a large load. This manuscript distinguishes disposable harmonic gear from conventional harmonic gear in terms of the application environment and structure. Then, this paper determines the single-tooth stiffness of the disposable harmonic gear under full load by using the non-uniform beam model and the improved energy method. In addition, the multi-tooth meshing in the disposable harmonic drive is considered, and the improved energy method is modified. Besides, the normal contact force and comprehensive elastic displacement at each meshing position are calculated according to the finite element model. Additionally, curves of the single-tooth stiffness and the comprehensive meshing stiffness are obtained. The theoretical results of the modified analytical method and FEM are compared to verify the correctness of the proposed method in terms of calculating the meshing stiffness of the disposable harmonic drive. Finally, FEM is used to obtain the failure form of the disposable harmonic gear under overload.

The aim of this study is to investigate the influencing factors associated with no/low response to preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) patients. A total of 79 patients were included in this prospective study. Fifteen factors that might affect the resistance to CCRT were included in this logistic regression analysis, these factors include the general clinical data of patients, the expression status of tumor stem cell marker CD44v6 and the volumetric imaging parameters of primary tumor lesions. We found that the no/low response status to preoperative CCRT was positively correlated with the real tumor volume (RTV), the total surface area of tumor (TSA), and CD44v6 expression, whereas negatively correlated with the tumor compactness (TC). According to the results of logistic regression analysis, two formulas that could predict whether or not no/low response to preoperative CCRT were established. The Area Under Curve (AUC) of the two formulas and those significant measurement data (RTV, TC, TSA) were 0.900, 0.858, 0.771, 0.754, 0.859, the sensitivity were 95.8%, 79.17%, 62.50%, 95.83%, 62.5%, the specificity were 70.9%, 74.55%, 83.64%,47.27%, 96.36%, the positive predictive values were 58.96%, 57.58%, 62.51%,44.23%, 88.23%, the negative predictive values were 97.48%, 89.13%, 83.64%, 96.29%, and 85.48%, respectively.

Mechanical equipment that will not be reused is defined as disposable machinery. Disposable harmonic drives (HDs) are commonly used in the field of aerospace and are sensitive to payloads. Reasonable calculation of the gear strength is essential for structural design. A method of calculating the contact characteristics of HDs under full load by combining a surface contact model with a three-dimensional finite element model (FEM) is proposed in this work. The mathematical model was established for calculating the no-load backlash of conventional and disposable harmonic gears after assembly. Afterward, the tooth load distribution and surface contact stress were determined using the Hertz contact theory. Finally, ABAQUS software was used to establish the FEM of the disposable HD, and the results were compared with those obtained from the theoretical model. The results revealed that the disposable harmonic gear can realize short-term transmission under full load.

The performance of aerostatic spindle is highly affected by the fluid–structure interaction effect between solid structure and air film. In working condition, the viscous heat generated by air film also influences the spindle performance greatly. In this article, the structure deformation induced by pressurized air film and viscous heat is investigated based on a multi-physics coupling model. The simulation results indicate that the structure deformation could lower the load-carrying capacity of air bearing. The reliability of proposed model is verified by experiments.

Hypoxic microenvironment and glutathione (GSH) accumulation in tumours limit the efficacy of cytotoxic reactive oxygen species (ROS) anti-tumour therapy. To address this challenge, we increased the consumption of GSH and the production of ROS through a novel nanoplatform with the action of inorganic nanoenzymes. In this study, we prepared mesoporous FeS2 using a simple template method, efficiently loaded AIPH, and assembled Ti3C2/FeS2-AIPH@BSA (TFAB) nanocomposites through selfassembly with BSA and 2D Ti3C2. The constructed TFAB nanotherapeutic platform enhanced chemodynamic therapy (CDT) by generating toxic hydroxyl radicals (OH) via FeS2, while consuming GSH to reduce the loss of generated OH via glutathione oxidase-like (GSH-OXD). In addition, TFAB is able to stimulate the decomposition of AIPH under 808 nm laser irradiation to produce oxygenindependent biotoxic alkyl radicals (R) for thermodynamic therapy (TDT). In conclusion, TFAB represents an innovative nanoplatform that effectively addresses the limitations of free radical-based treatment strategies. Through the synergistic therapeutic strategy of photothermal therapy (PTT), CDT, and TDT within the tumor microenvironment, TFAB nanoplatforms achieve controlled AIPH release, ROS generation, intracellular GSH consumption, and precise temperature elevation, resulting in enhanced intracellular oxidative stress, significant apoptotic cell death, and notable tumor growth inhibition. This comprehensive treatment strategy shows great promise in the field of tumor therapy [ABSTRACT FROM AUTHOR]