Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.

Case report: A lung squamous cell carcinoma patient with a rare EGFR G719X mutation and high PD-L1 expression showed a good response to anti-PD1 therapy.

Lung cancer treatment has transitioned fully into the era of immunotherapy, yielding substantial improvements in survival rate for patients with advanced non-small cell lung cancer (NSCLC). In this report, we present a case featuring a rare epidermal growth factor receptor (EGFR) mutation accompanied by high programmed death-ligand 1 (PD-L1) expression, demonstrating remarkable therapeutic efficacy through a combination of immunotherapy and chemotherapy. A 77-year-old male with no family history of cancer suffered from upper abdominal pain for more than half months in August 2020 and was diagnosed with stage IV (cT3N3M1c) lung squamous cell carcinoma (LUSC) harboring both a rare EGFR p.G719C mutation and high expression of PD-L1 (tumor proportion score [TPS] = 90%). Treatment with the second-generation targeted therapy drug Afatinib was initiated on September 25, 2020. However, resistance ensued after 1.5 months of treatment. On November 17, 2020, immunotherapy was combined with chemotherapy (Sintilimab + Albumin-bound paclitaxel + Cisplatin), and a CT scan conducted three months later revealed significant tumor regression with a favorable therapeutic effect. Subsequently, the patient received one year of maintenance therapy with Sintilimab, with follow-up CT scans demonstrating subtle tumor shrinkage (stable disease). This case provides evidence for the feasibility and efficacy of immunotherapy combined with chemotherapy in the treatment of EGFR-mutated and PD-L1 highly expressed LUSC.

SGT++: Improved Scene Graph-Guided Transformer for Surgical Report Generation.

Automatically recording surgical procedures and generating surgical reports are crucial for alleviating surgeons' workload and enabling them to concentrate more on the operations. Despite some achievements, there still exist several issues for the previous works: 1) failure to model the interactive relationship between surgical instruments and tissue; and 2) neglect of fine-grained differences within different surgical images in the same surgery. To address these two issues, we propose an improved scene graph-guided Transformer, also named by SGT++, to generate more accurate surgical report, in which the complex interactions between surgical instruments and tissue are learnt from both explicit and implicit perspectives. Specifically, to facilitate the understanding of the surgical scene graph under a graph learning framework, a simple yet effective approach is proposed for homogenizing the input heterogeneous scene graph. For the homogeneous scene graph that contains explicit structured and fine-grained semantic relationships, we design an attention-induced graph transformer for node aggregation via an explicit relation-aware encoder. In addition, to characterize the implicit relationships about the instrument, tissue, and the interaction between them, the implicit relational attention is proposed to take full advantage of the prior knowledge from the interactional prototype memory. With the learnt explicit and implicit relation-aware representations, they are then coalesced to obtain the fused relation-aware representations contributing to generating reports. Some comprehensive experiments on two surgical datasets show that the proposed STG++ model achieves state-of-the-art results.

Diversities of disability caused by lung cancer in the 66 Belt and Road initiative countries: a secondary analysis from the Global Burden of Disease Study 2019.

Objectives: Due to the increase in life expectancy and the aging of the global population, the "Belt and Road" ("B&R") countries are faced with varying degrees of lung cancer threat. The purpose of this study is to analyze the differences in the burden and trend of lung cancer disability in the "B&R" countries from 1990 to 2019 so as to provide an analytical strategic basis to build a healthy "B&R". Methods: Data were derived from the Global Burden of Disease 2019 (GBD 2019). Incidence, mortality, prevalence, the years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lung cancer and those attributable to different risk factors were measured from 1990 to 2019. Trends of disease burden were estimated by using the average annual percent change (AAPC), and the 95% uncertainty interval (UI) was reported. Results: China, India, and the Russian Federation were the three countries with the highest burden of lung cancer in 2019. From 1990 to 2019, the AAPC of incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), most countries in North Africa, and the Middle East, the trend was mainly upward. The AAPC of age-standardized incidence was 1.33% (1.15%-1.50%); the AAPC of prevalence, mortality, and DALYs from lung cancer in China increased by 24% (2.10%-2.38%), 0.94% (0.74%-1.14%), and 0.42% (0.25%-0.59%), respectively. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the vast majority of "B&R" countries, but for women, most countries had an upward trend. For adults aged 75 years or older, the age-standardized YLD rate showed an increasing trend in most of the "B&R" countries. Except for the DALY rate of lung cancer attributable to metabolic risks, a downward trend of the DALY rate attributable to all risk factors, behavioral risks, and environmental/occupational risks was shown in the vast majority of "B&R" countries. Conclusion: The burden of lung cancer in "B&R" countries varied significantly between regions, genders, and risk factors. Strengthening health cooperation among the "B&R" countries will help to jointly build a community with a shared future for mankind.

A case report of membrane induction combined with RIA technique for the repair of distal humerus segmentary bone defect.

Bone nonunion and bone defect are common postoperative complications in clinic. Membrane induction or Ilizarov technique is often used to repair bone defect. Autologous bone is often used for bone defect repair and reconstruction, and the anterior superior iliac spine, posterior superior iliac spine or fibula bone is used as the donor area for bone extraction, but there are problems of donor area complications. In recent years, the development of bone marrow aspiration (RIA) has provided a new alternative way for the source of autogenous bone. We report a 48-year-old female patient with a comminuted supracondylar intercondylar fracture of the left humerus due to a car accident. After 8 months of emergency debridement and suture with Kirschner wire internal fixation, the fracture was found to be unhealed with extensive bone defects. We used membrane induction combined with RIA technology to repair and reconstruct the patients, and found good osteogenesis through late follow-up. In theory, membrane induction technique can realize the reconstruction of large segmental bone defects, but the scope of repair is often limited by the lack of autologous bone source. The emergence and development of RIA technology provides us with a new autologous bone donor area for bone repair and reconstruction surgery. It can provide a large amount of high-quality cancellar bone mud through minimally invasive means. Meanwhile, it can reduce patients' pain, infection, fracture, aesthetics and other problems caused by iliac bone extraction, and shorten patients' bed time. Maximize the preservation of the patient's autologous bone source. For the first time in the world, we reported the combination of membrane induction technology and RIA technology in the treatment of segmental bone defects, providing a new idea for the treatment of bone defects.

Single-Atom Cu Stabilized on Ultrathin WO2.72 Nanowire for Highly Selective and Ultrasensitive ppb-Level Toluene Detection.

Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ-annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra /Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single-atom catalysts (SACs)-containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic-level interface regulation engineering of WO2.72 nanowire-supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

Cooperative dual medical ontology representation learning for clinical assisted decision-making.

OBJECTIVE: Predicting clinical events and providing assisted decision-making using Electronic Health Records (EHRs) play a central role in personalized healthcare. Despite the promising performance achieved for diagnosis and procedure predictions, most of the existing predictive models regard different medical codes as the same type and generally ignore the dependence between diagnoses and procedures in patients' admission history. To address these issues, we propose an end-to-end cooperative dual medical ontology representation learning framework for clinical assisted decision-making. MATERIALS AND METHODS: The framework consists of two primary modules: (1) dual medical ontology representation learning to facilitate the learning of medical concepts and (2) task dependent multi-task prediction to capture the correlation between diagnoses and procedures in patients' admission history. We evaluate our method with EHRs from the MIMIC-III Clinical Database, covering 6321 patients and 16335 visits. RESULTS: Experiments conducted on the MIMIC-III dataset show that the proposed model achieves the best performance, with a top-20 accuracy of 58.20% for diagnosis prediction and a top-20 accuracy of 75.85% for procedure prediction. In addition, a series of experimental analyses and case studies further illustrate the excellent performance of our model. CONCLUSION: We propose an end-to-end cooperative dual medical ontology representation learning framework, which achieves superior performance on multi-task diagnosis and procedure predictions. The source code is available at https://github.com/mhxu1998/CoDMO.

Efficacy comparison of antibiotic bone cement-coated implants and external fixations for treating infected bone defects.

PURPOSE: This study aimed to investigate the clinical efficacy of antibiotic bone cement-coated implants compared with external fixations for treating infected bone defects. METHODS: We retrospectively enrolled 119 patients with infected bone defects in our hospital from January 2010 to June 2021, of which 56 were treated with antibiotic bone cement-coated implants and 63 were with external fixation. RESULTS: The pre-operative and post-operative haematological indexes were tested to assess the infection control; the post-operative CRP level in the internal fixation group was lower than that in the external fixation group. No statistical significance was found in the rate of infection recurrence, loosening and rupture of the fixation, and amputation between the two groups. Twelve patients in the external fixation group had pin tract infection. In the evaluation of the Paley score scale, bone healing aspect revealed no significant difference between the two groups, while in the limb function aspect, antibiotic cement-coated implant group showed a much better score than the external fixation group (P = 0.002). The anxiety evaluation scale result also showed lower score in the antibiotic cement implant group (P < 0.001). CONCLUSIONS: Compared with external fixation, antibiotic bone cement-coated implant had the same effect on controlling infection and was more effective in recovering limb function and mental health in the first-stage treatment of infected bone defects after debridement.

CED: A case-level explainable paramedical diagnosis via AdaGBDT.

OBJECTIVE: The rapid growth of medical data has greatly promoted the wide exploitation of machine learning for paramedical diagnosis. Inversely proportional to their performance, most machine learning models generally suffer from the lack of explainability, especially the local explainability of the model, that is, the case-specific explainability. MATERIALS AND METHODS: In this paper, we proposed a GBDT (Gradient Boosting Decision Tree)-based explainable model for case-specific paramedical diagnostics, and mainly make the following contributions: (1) an adaptive gradient boosting decision tree (AdaGBDT) model is proposed to boost the path-mining for decision effectively; (2) to learn a case-specific feature importance embedding for a specific patient, the bi-side mutual information is applied to characterize the backtracking on the decision path; (3) through the collaborative decision-making by globally explainable AdaGBDT with case-based reasoning (CBR) in the case-specific metric space, some hard cases can be identified by the means of visualized interpretation. The performance of our model is evaluated on the Wisconsin diagnostic breast cancer dataset and the UCI heart disease dataset. RESULTS: Experiments conducted on two datasets show that our AdaGBDT achieves the best performance, with the F1-value of 0.9647 and 0.8405 respectively. Moreover, a series of experimental analyses and case studies further illustrate the excellent performance of feature importance embedding. CONCLUSION: The proposed case-specific explainable paramedical diagnosis via AdaGBDT has excellent predictive performance, with both promising case-level and consistent global explainability.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Multi-Modal Graph Learning for Disease Prediction.

Benefiting from the powerful expressive capability of graphs, graph-based approaches have been popularly applied to handle multi-modal medical data and achieved impressive performance in various biomedical applications. For disease prediction tasks, most existing graph-based methods tend to define the graph manually based on specified modality (e.g., demographic information), and then integrated other modalities to obtain the patient representation by Graph Representation Learning (GRL). However, constructing an appropriate graph in advance is not a simple matter for these methods. Meanwhile, the complex correlation between modalities is ignored. These factors inevitably yield the inadequacy of providing sufficient information about the patient's condition for a reliable diagnosis. To this end, we propose an end-to-end Multi-modal Graph Learning framework (MMGL) for disease prediction with multi-modality. To effectively exploit the rich information across multi-modality associated with the disease, modality-aware representation learning is proposed to aggregate the features of each modality by leveraging the correlation and complementarity between the modalities. Furthermore, instead of defining the graph manually, the latent graph structure is captured through an effective way of adaptive graph learning. It could be jointly optimized with the prediction model, thus revealing the intrinsic connections among samples. Our model is also applicable to the scenario of inductive learning for those unseen data. An extensive group of experiments on two disease prediction tasks demonstrates that the proposed MMGL achieves more favorable performance. The code of MMGL is available at https://github.com/SsGood/MMGL.

Predictive role of the monocyte-to-lymphocyte ratio in advanced hepatocellular carcinoma patients receiving anti-PD-1 therapy.

Background: The immune checkpoint inhibitor (ICIs) therapy has been proven effective in a range of solid tumors including hepatocellular carcinoma (HCC), non-small cell lung carcinoma and metastatic melanoma. However, only a subset of approximately 20% of patients shows an objective response to anti-PD-1 therapy in HCC. Furthermore, the response to anti-PD-1 therapy is not correlated with programmed cell death 1 ligand expression in tumor tissue. Therefore, it is urgent to identify a biomarker to predict the response of anti-PD-1 therapy. Methods: This retrospective study was conducted at the Fudan University Shanghai Cancer Center from December 2019 to June 2021. The monocyte-to-lymphocyte ratio (MLR) was analyzed using a receiver operating characteristic (ROC) curve. A Cox regression model and the log-rank test were used to analyze the relationship between the MLR value and the time to progression (TTP). Results: A total of 34 advanced HCC patients were enrolled in this study. The cut-off point for the MLR at baseline was 0.35. Univariate and multivariate Cox regression models showed that the MLR at baseline was significantly correlated with the TTP (P<0.05). Consistent results were found for disease progression. The log-rank test showed that patients in the low MLR group had a longer TTP (P=0.0027). At the time of disease progression, the median TTP in the low and high MLR groups were 33 and 18 weeks, respectively (P=0.0047). Conclusions: The MLR can predict the response to anti-PD-1 therapy, and a high MLR is correlated with a short TTP in anti-PD-1-treated HCC patients.

A novel gene functional similarity calculation model by utilizing the specificity of terms and relationships in gene ontology.

BACKGROUND: Recently, with the foundation and development of gene ontology (GO) resources, numerous works have been proposed to compute functional similarity of genes and achieved series of successes in some research fields. Focusing on the calculation of the information content (IC) of terms is the main idea of these methods, which is essential for measuring functional similarity of genes. However, most approaches have some deficiencies, especially when measuring the IC of both GO terms and their corresponding annotated term sets. To this end, measuring functional similarity of genes accurately is still challenging. RESULTS: In this article, we proposed a novel gene functional similarity calculation method, which especially encapsulates the specificity of terms and edges (STE). The proposed method mainly contains three steps. Firstly, a novel computing model is put forward to compute the IC of terms. This model has the ability to exploit the specific structural information of GO terms. Secondly, the IC of term sets are computed by capturing the genetic structure between the terms contained in the set. Lastly, we measure the gene functional similarity according to the IC overlap ratio of the corresponding annotated genes sets. The proposed method accurately measures the IC of not only GO terms but also the annotated term sets by leveraging the specificity of edges in the GO graph. CONCLUSIONS: We conduct experiments on gene functional classification in biological pathways, gene expression datasets, and protein-protein interaction datasets. Extensive experimental results show the better performances of our proposed STE against several baseline methods.

Margin Preserving Self-Paced Contrastive Learning Towards Domain Adaptation for Medical Image Segmentation.

To bridge the gap between the source and target domains in unsupervised domain adaptation (UDA), the most common strategy puts focus on matching the marginal distributions in the feature space through adversarial learning. However, such category-agnostic global alignment lacks of exploiting the class-level joint distributions, causing the aligned distribution less discriminative. To address this issue, we propose in this paper a novel margin preserving self-paced contrastive Learning (MPSCL) model for cross-modal medical image segmentation. Unlike the conventional construction of contrastive pairs in contrastive learning, the domain-adaptive category prototypes are utilized to constitute the positive and negative sample pairs. With the guidance of progressively refined semantic prototypes, a novel margin preserving contrastive loss is proposed to boost the discriminability of embedded representation space. To enhance the supervision for contrastive learning, more informative pseudo-labels are generated in target domain in a self-paced way, thus benefiting the category-aware distribution alignment for UDA. Furthermore, the domain-invariant representations are learned through joint contrastive learning between the two domains. Extensive experiments on cross-modal cardiac segmentation tasks demonstrate that MPSCL significantly improves semantic segmentation performance, and outperforms a wide variety of state-of-the-art methods by a large margin.

Analysis of the epidemiological status, microbiology, treatment methods and financial burden of hematogenous osteomyelitis based on 259 patients in Northwest China.

Background: The incidence of hematogenous osteomyelitis is on the rise, and the prognosis is poor. There has been no large-scale epidemiological analysis of hematogenous osteomyelitis in the world, and the treatment method is still controversial. Methods: A retrospective case study method was used to collect and analyze clinical data obtained from patients with hematogenous osteomyelitis in a tertiary hospital in Northwest China from January 1, 2011, to December 31, 2020. The aim of this study was to investigate the epidemiological status, microbiological characteristics, treatment and financial burden of hematogenous osteomyelitis in Northwest China to explore the therapeutic effects of different treatment methods, elucidate the epidemiological characteristics of hematogenous osteomyelitis and to provide a basis for the choice of treatment. Results: We included 259 patients with hematogenous osteomyelitis, including 96 patients with acute hematogenous osteomyelitis and 163 patients with chronic hematogenous osteomyelitis. The cause of the disease was not obvious in most patients, the sex ratio of males to females was 1.98, and the three most common infected sites were the tibia, femur and phalanx. Regarding preoperative serum inflammatory markers, the rate of positivity for ESR was the highest at 67.58%. Among pathogenic microorganisms, Staphylococcus aureus was the most common. Regarding the financial burden, the median total cost per patient was 25,754 RMB, and medications accounted for the largest proportion of the main costs. Conclusions: The most common pathogen associated with HO infection was MSSA. Oxacillin has good PK and PD and is recommended as the first-line drug. Some blood-borne bone infections may lead to complications, such as pulmonary infection through bacteremia, which requires early detection to avoid a missed diagnosis. Regarding surgical intervention, debridement plus absorbable calcium sulfate bone cement and calcium sulfate calcium phosphate bone cement exclusion have achieved good therapeutic effects, but they are worthy of further in-depth research. Regarding the financial burden, the median total cost per patient was 25,754 RMB. The financial burden of blood-borne osteomyelitis was lower than that of traumatic osteomyelitis. Among the main costs, drugs accounted for the largest proportion.

Thermodynamically driven metal diffusion strategy for controlled synthesis of high-entropy alloy electrocatalysts.

We report a thermodynamically driven metal diffusion strategy for the controlled synthesis of high-entropy alloy (HEA) nanocrystals using electrospun carbon nanofibers (CNFs) as nanoreactors. This conceptual pathway is resistant to high temperatures and produces a series of medium-entropy alloy (MEA) and HEA nanocrystals supported on CNFs by adjusting the numbers and kinds of elements. The FeCoNiCrMn/CNFs obtained the lowest overpotential of 345 mV at 50 mA cm-2 compared to MEA. The operando electrochemical Raman results indicate that the enhanced electron transfer from low-electronegativity Fe, Ni, Cr and Mn to the orbit of the Co atom makes Co a local negative charge center, leading to the decrease in absorption energy of OH.

Custom-Made Antibiotic Cement-Coated Nail for the Treatment of Infected Bone Defect.

BACKGROUND: Longbone infected bone defect remains a great challenge due to multiple surgeries, long-term treatment duration, and uncertain prognosis. Treatment principles include eradication/debridement, stabilization, and antibiotic administration. An antibiotic cement-coated nail has shown great prospects due to both local antibiotic elution and stabilization of bone defects. However, the current fabrication technique remains to be improved. METHODS: For the first time, we described a new method for custom-made cement-coated nail fabrication based on a 3D printing technique. A retrospective study of 19 consecutive patients with long bone infected bone defects from one medical center was conducted who met the inclusion and exclusion criteria from November 2016 to May 2020. The treatment involved thorough debridement, custom-made antibiotic cement-coated nail filling, and culture-specific systemic antibiotic treatment guided by a multidisciplinary team. Clinical and radiographic examinations (X-ray and CT scans) were used to evaluate bony union. Clinical and laboratory examinations were used to evaluate the infection control. The SF-36 score was used to evaluate patients' quality of life pre- and postoperatively. RESULTS: The mean follow-up was 98.8 weeks (ranging from 40 to 192). All cases achieved infection control, 3 cases achieved bone healing after one-stage operation, and 12 cases achieved bone healing after a two-stage bone graft procedure. At the last follow-up, none of the 19 patients had infection recurrence or 1 case had failure of the protective plate. The pre- and postoperative SF-36 score showed that there were statistical differences in all the 9 aspects. CONCLUSIONS: The precise custom-made antibiotic cement-coated intramedullary nail through the 3D printing technique used in this study is an effective strategy for the treatment of infected bone defects of long bone. This technique may help to increase the infection control rate and promote bone healing.

WITHDRAWN: Circ_0000517 contributes to hepatocellular carcinoma progression by upregulating ARID4B via sponging miR-328-3p.

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LHPP suppresses tumorigenesis of intrahepatic cholangiocarcinoma by inhibiting the TGFß/smad signaling pathway.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a histidine phosphatase, plays an important role in tumor progression and metastasis as a tumor suppressor. Here, we investigate the effect of LHPP in intrahepatic cholangiocarcinoma (ICC). We discovered that LHPP was downregulated in tumor tissues and low levels of LHPP predicted poor survival. LHPP inhibited ICC cell growth, cell invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanically, LHPP deactivated transforming growth factor­beta (TGFß) signaling pathway, and low level LHPP upregulated the expression of TGFß and phosphorylation of smad2/3. Moreover, inhibition of this pathway reversed the biofunction of LHPP. In summary, these findings demonstrated that LHPP suppressed ICC through inhibiting the activation of TGFß/smad signaling. Our results indicated that LHPP is a potential therapeutic target in ICC.

Comparing the Population Pharmacokinetics of and Acute Kidney Injury Due to Polymyxin B in Chinese Patients with or without Renal Insufficiency.

Despite excellent bactericidal effect, dosing adjustment of polymyxin B for patients with renal insufficiency and polymyxin B-related nephrotoxicity is still a major concern to clinicians. The aim of this study was to compare the population pharmacokinetics (PK) properties of polymyxin B in Chinese patients with different renal functions and to investigate the relationship between PK parameters and polymyxin B-related acute kidney injury (AKI). A total of 37 patients with normal renal function (creatinine clearance ≥ 80 ml/min) and 33 with renal insufficiency (creatinine clearance < 80 ml/min) were included. In the two-compartment population PK models, the central compartment clearance (CL) (2.19 liters/h versus 1.58 liters/h; P < 0.001) and intercompartmental clearance (Q) (13.83 liters/h versus 10.28 liters/h; P < 0.001) values were significantly different between the two groups. The simulated values for AUC across 24 h at steady state (AUCss,24h) for patients with normal renal function were higher than those for patients with renal insufficiency. However, renal dosing adjustment of polymyxin B seemed not to be necessary. In addition, during the treatment, AKI occurred in 23 (32.86%) patients. The polymyxin B AUCss,24h in patients with AKI was significantly higher than that in patients without AKI (108.66 ± 70.10 mg · h/liter versus 66.18 ± 34.79 mg · h/liter; P = 0.001). Both the receiver operating characteristic (ROC) curve and logistic regression analysis showed that an AUCss,24h of >100 mg · h/liter was a good predictor for the probability of nephrotoxicity.