Ex-vivo Liver Resection and Autotransplantation for Liver Malignancy: A Large Volume Retrospective Clinical Study.

OBJECTIVE: To assess the effectiveness of optimized ex-vivo liver resection and autotransplantation (ELRA) for treating liver malignancies. SUMMARY BACKGROUND DATA: ELRA is a promising surgery for radical resection of conventionally unresectable tumors, despite the disappointing long-term prognosis during its' developmental stages. A recent multicenter study reported 5-year overall and disease-free survival rates (OS, DFS) of 28% and 20.8%, respectively. METHODS: We retrospectively analyzed data of patients who underwent ELRA for advanced liver cancers between 2009 and 2022. We applied ELRA via our novel surgical indication classification system where the surgical risk with curative intent for advanced liver malignancy was controllable using the ex-vivo approach. The ELRA was optimized for determinacy, predictability, and controllability via the precision liver surgery paradigm (PLS). RESULTS: Thirty-seven cases with liver malignancies were enrolled. The operative time and anhepatic phase duration were 649.6±200.0 and 261.2±74.5 min, respectively, while the intraoperative blood loss was 1902±1192 mL. Negative resection margins were achieved in all patients, and the 90-day morbidity at Clavien-Dindo IIIa/IIIb and mortality rates were 27.0% and 24.3%. Post-ELRA 1-, 3-, and 5-year actual OS rates were 62.2%, 37.8%, and 35.1%, respectively, and 1-, 3-, and 5-year actual DFS were 43.2%, 24.3%, and 18.9%, respectively. CONCLUSIONS: Long-term outcomes of ELRA under the PLS for advanced liver malignancy were favorable. Appropriate criteria for disease selection & surgical indications and optimized procedures together can improve surgical treatment and patient prognosis.

Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with adenomyomatous hyperplasia of the Vaterian system: a single-centre study from China.

BACKGROUND: The relationship between adenomyomatous hyperplasia of the Vaterian system(AV) and cancer is unclear, some reports suggest that AV is often combined with mucosal glandular dysplasia, but it is not clear whether mucosal glandular dysplasia is a risk factor for carcinogenesis of AV. The aim of this study was to retrospective analysis of role of ductal glandular dysplasia as a risk factor in the development of carcinoma in AV. METHODS: A total of 328 cases who underwent surgery with a final pathological diagnosis of adenomyomatous hyperplasia (AH) in the Chinese PLA General Hospital in BeiJing, China, between January 2005 and December 2021 were retrospectively collected. There were Seventeen cases(5%) in which the lesions were located in the common bile duct as well as the ampulla of Vater, and their clinical (age, sex, etc.), imaging (cholelithiasis, etc.) and pathological data (mucosal glandular dysplasia, etc.) were collected. Clinical data and pathological features of AV with or without mucosal glandular dysplasia were analyzed. RESULTS: There were 17 out of 328 cases of AH occurring in the Vaterian system (5%). Three of seventeen AV cases were associated with carcinoma (18%). Of three cases, two (12%) with the tumor lesions in the mucosal glands adjacent to the AH (biliary tract cancer and ampullary cancer), and one (6%) with carcinoma developed from AH itself in the ampulla of Vater. All carcinomas had adenomyomatous hyperplasia with nearby mucosal glandular dysplasia (MGD). The percentage of BTC or AC was higher in patients with concurrent AH and MGD compared to AH patients without MGD. The results show tendency toward statistical significance (P = 0.082). This difference was more obvious among AH with severe dysplasia compared to adenomyomatous hyperplasia with mild-moderate dysplasia (P = 0.018). CONCLUSION: This study is the first to find that AV is associated with biliary tract cancer and ampullary cancer. In AV, the mucosal glandular dysplasia may be a risk factor for the development of malignancy. The underlying mechanism for carcinogenesis of AV could be AH itself or its secretions stimulating mucosal glands hyperplasia, then mucosal glands dysplasia. AV may be a precancerous lesion.

Comparison of survival benefit between salvage surgery after conversion therapy versus surgery alone for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

BACKGROUND: Salvage surgery after conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody has shown improved survival benefits in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We aimed to compare the survival benefits in a retrospective cohort of patients with HCC with PVTT who underwent salvage surgery after conversion therapy and surgery alone. METHODS: From January 2015 to October 2021, we selected patients diagnosed with HCC with PVTT who underwent liver resection at Chinese PLA General Hospital. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. RESULTS: The 6-, 12-, and 24-month recurrence-free survival rates in the conversion and surgery alone groups were 80.3% vs 36.5%, 65.4% vs 29.4%, and 56% vs 21%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. CONCLUSIONS: For patients with HCC with PVTT, surgery after conversion therapy is in relationship with increased survival in comparison with surgery alone.

Roles of BATF/JUN/IRF4 complex in tacrolimus mediated immunosuppression on Tfh cells in acute rejection after liver transplantation.

Rejection injury is a serious complication after liver transplantation (LTx). Tacrolimus (Tac) is a key immunosuppressive agent in the prevention of liver rejection after transplantation. The basic leucine zipper ATF-like transcription factor (BATF)/JUN/interferon regulatory factor 4 (IRF4) complex serves critical functions in the immune response. This study aimed to explore the role of the BATF/JUN/IRF4 complex in rejection after LTx by treatment with Tac. Herein, DA and Lewis (LEW) rats were used to construct the LTx animal model. The recipient LEW rats were treated with Tac or saline, subcutaneously. Splenic mononuclear cells were treated with Tac at 1 and 10 nM after stimulation with interleukin-6 (IL-6), and the expression of factors associated with the nuclear factor of activated T cells (NFAT)-BATF/JUN/IRF4 and IL-21 were detected. The results demonstrated that Tac prolonged the allografts survival and attenuated inflammation injury, and decreased the percentage frequencies of T follicular helper (Tfh) cells in peripheral blood mononuclear cells and inhibited B-cell lymphoma 6 (Bcl-6) and IL-6 expression in Tfh cells. In addition, Tac inhibited the expression of the BATF/JUN/IRF4 complex, Bcl-6 and IL-21 NFATc1 and NFATc2 were inhibited by Tac, and interacted with the promoter of BATF and IRF4. In conclusion, the attenuation of rejection injury may be dependent on the NFAT-BATF/JUN/IRF4-IL-21 axis, and the BATF/JUN/IRF4 complex participates in the inhibition of IL-21-producing Tfh cells after treatment with Tac. These findings suggest that the BATF/JUN/IRF4 complex-IL-21 axis may be used as a potential target for attenuating rejection injury after LTx.

Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa-miR-23b-3p/KCND2 axis.

Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa-miR-23b-3p (miR-23b-3p), and KCND2 were detected by qRT-RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK-8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual-luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR-23b-3p, and KCND2. Furthermore, the levels of the EMT-associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR-23b-3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR-23b-3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.

Faster-than-Nyquist non-orthogonal frequency-division multiplexing based on fractional Hartley transform: erratum.

This erratum is presented to correct the errors in our paper [Opt. Lett.41, 4488 (2016) OPLEDP0146-959210.1364/OL.41.004488].

Faster-than-Nyquist non-orthogonal frequency-division multiplexing based on fractional Hartley transform.

In this Letter, we propose, to the best of our knowledge, the first faster-than-Nyquist non-orthogonal frequency-division multiplexing based on fractional Hartley transform (FrHT). Different from the existing NOFDM signal, the real-valued FrHT-based NOFDM signal can be directly applied to an intensity-modulated/direct-detection optical system without upconversion, and it can achieve a transmission rate faster than the Nyquist rate, which is the up limit of orthogonal frequency-division multiplexing. For example, when bandwidth compression factor α is set to 0.4, the transmission rate is 20 percent faster than the Nyquist rate. Furthermore, we demonstrate simulations and experiments to verify the feasibility of FrHT-based NOFDM. After a 25 km standard single-mode fiber transmission, the bit error rate of FrHT-based DC-offset NOFDM can achieve a 7% and 20% forward error correction limit when α is set to 0.45 and 0.4, respectively.

Potential application of gasification to recycle food waste and rehabilitate acidic soil from secondary forests on degraded land in Southeast Asia.

Gasification is recognized as a green technology as it can harness energy from biomass in the form of syngas without causing severe environmental impacts, yet producing valuable solid residues that can be utilized in other applications. In this study, the feasibility of co-gasification of woody biomass and food waste in different proportions was investigated using a fixed-bed downdraft gasifier. Subsequently, the capability of biochar derived from gasification of woody biomass in the rehabilitation of soil from tropical secondary forests on degraded land (adinandra belukar) was also explored through a water spinach cultivation study using soil-biochar mixtures of different ratios. Gasification of a 60:40 wood waste-food waste mixture (w/w) produced syngas with the highest lower heating value (LHV) 5.29 MJ/m(3)-approximately 0.4-4.0% higher than gasification of 70:30 or 80:20 mixtures, or pure wood waste. Meanwhile, water spinach cultivated in a 2:1 soil-biochar mixture exhibited the best growth performance in terms of height (a 4-fold increment), weight (a 10-fold increment) and leaf surface area (a 5-fold increment) after 8 weeks of cultivation, owing to the high porosity, surface area, nutrient content and alkalinity of biochar. It is concluded that gasification may be an alternative technology to food waste disposal through co-gasification with woody biomass, and that gasification derived biochar is suitable for use as an amendment for the nutrient-poor, acidic soil of adinandra belukar.

Vitamin E intake and pancreatic cancer risk: a meta-analysis of observational studies.

BACKGROUND: Some epidemiological studies have suggested that vitamin E intake reduces the risk of pancreatic cancer; however, this conclusion has not been supported by all the published studies. We conducted a meta-analysis to assess the relationship between vitamin E intake and the risk of pancreatic cancer by combining the results from published articles. MATERIAL/METHODS: We searched the published studies that reported the relationship between vitamin E intake and pancreatic cancer risk using the PubMed, Web of Science, and Embase databases through December 31st, 2014. Based on a fixed-effects or random-effects model, the RR and 95% CI were used to assess the combined risk. RESULTS: In total, 10 observational studies (6 case-control studies and 4 cohort studies) were included. The overall RR (95% CI) of pancreatic cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.73, 0.89). We found little evidence of heterogeneity (I2=19.8%, P=0.255). In the subgroup analyses, we found an inverse association between vitamin E intake and pancreatic cancer risk both in the case-control and cohort studies. Additionally, this inverse association was not modified by different populations. CONCLUSIONS: In our meta-analysis, there was an inverse association between vitamin E intake and the risk of pancreatic cancer. A high level of vitamin E might be a protective factor for populations at risk for pancreatic cancer.

Leukocyte immunoglobulin-like receptor B4: A keystone in immune modulation and therapeutic target in cancer and beyond.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) significantly impacts immune regulation and the pathogenesis and progression of various cancers. This review discusses LILRB4's structural attributes, expression patterns in immune cells, and molecular mechanisms in modulating immune responses. We describe the influence of LILRB4 on T cells, dendritic cells, NK cells, and macrophages, and its dual role in stimulating and suppressing immune activities. The review discusses the current research on LILRB4's involvement in acute myeloid leukemia, chronic lymphocytic leukemia, and solid tumors, such as colorectal cancer, pancreatic cancer, non-small cell lung cancer, hepatocellular carcinoma, and extramedullary multiple myeloma. The review also describes LILRB4's role in autoimmune disorders, infectious diseases, and other conditions. We evaluate the recent advancements in targeting LILRB4 using monoclonal antibodies and peptide inhibitors and their therapeutic potential in cancer treatment. Together, these studies underscore the need for further research on LILRB4's interactions in the tumor microenvironment and highlight its importance as a therapeutic target in oncology and for future clinical innovations.

[Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury].

OBJECTIVE: To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assistance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury. METHODS: A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022. Among them, 39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of (44.98±7.33) years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy including 24 males and 13 females with an average age of (44.37±10.82) years old. Among them, 42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation (INFIX) or suprapubic support screws to fix the anterior pelvic ring. Postoperative follow-up time, operation time, complications of the two groups were compared. Results of Matta reduction criteria, Majed efficacy evaluation, the CT grading and the rate of secondary surgical revision were compared. RESULTS: The nailing time of (32.63±7.33) min in CT group was shorter than that of (52.95±10.64) min in C-arm group (t=-9.739, P<0.05). The follow-up time between CT group (11.97±1.86) months and C-arm group (12.03±1.71) months were not statistically significant(P>0.05). The postoperative complication rates between two groups were not statistically significant (χ2=0.159, P>0.05). Results of Matta reduction criteria (Z=2.79, P<0.05), Majeed efficacy evaluation(Z=2.79, P<0.05), CT grading (Z=2.83, P<0.05) in CT group were better than those in C-arm group(P<0.05); the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group (χ2=5.641, P<0.05). CONCLUSION: Compared with traditional C-arm fluoroscopy, intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time, high accuracy and safety, and significant decrease in postoperative secondary revision rate, and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Prediction of the prognosis after liver transplantation in severe hepatitis B-induced liver failure and clinical decision for liver transplantation.

BACKGROUND: Severe hepatitis B-induced liver failure (SHBLF) patients who require liver transplantation represent a particular challenge. We sought to explore the prognostic factors and establish a new scoring model, the SHBLF prognosis model (SHBLFPM), which can aid in clinical decision making. MATERIALS AND METHODS: A total of 98 patients who underwent liver transplantation for SHBLF in our center were retrospectively recruited between January 1, 1999, and December 31, 2010. The clinical and biochemical data were analyzed using the Cox proportional hazards model and log-rank test. The receiver operating characteristic curves were obtained for the King's College Hospital (KCH) criterion, the model for end-stage liver disease (MELD), and the new model; the areas under the curves were compared using a z-test. RESULTS: The independent factors predicting the prognosis were the age of the patient (AP, P = 0.017), hepatic encephalopathy (HE, P = 0.013), the serum total bilirubin concentration (TBiL, P < 0.001), and the international normalized ratio for prothrombin time (INR, P = 0.001), as identified using a multivariate Cox regression analysis. The area under the curve of the new regression model (0.881) was significantly larger than that of the MELD (0.783) and KCH scores (0.596) (P < 0.05). Patients with a preoperative SHBLFPM score <23.57 had a significantly better prognosis than those with higher scores (P < 0.001). CONCLUSIONS: Age of patient, hepatic encephalopathy, serum total bilirubin concentration, and international normalized ratio for prothrombin time are independent factors affecting the posttransplantation mortality of SHBLF patients. SHBLFPM may be a criterion for the clinical decision for liver transplantation in SHBLF patients with a greater prognostic predictive ability than the MELD and KCH models.

Effects of immunosuppressive agents on Th17 cells involved in transplantation.

The lymphocyte-derived helper T (Th) cells are critical regulators of the adaptive immune response and are associated with inflammatory disease. The most recently recognized Th-cell lineage, Th17, plays an important role in host defense against extracellular pathogens by secreting the proinflammatory cytokine, interleukin 17, and recruiting reactive oxygen species (ROS)-producing monocytes to the site of infection. However, accumulating evidence has implicated Th17-cell dysregulation as an underlying cause for some immune-related pathogenic conditions, including allograft rejection. Recent studies of human transplant patients have indicated that Th17 cells exhibit resistance to current immunosuppressive therapies that would otherwise prevent allograft rejection. In this review, we will discuss the most current research findings related to Th17-cell function in various kinds of allografts.

Synchronization of Delayed Memristor-Based Neural Networks via Pinning Control With Local Information.

In this article, a novel pinning control method, only requiring information from partial nodes, is developed to synchronize drive-response memristor-based neural networks (MNNs) with time delay. An improved mathematical model of MNNs is established to describe the dynamic behaviors of MNNs accurately. In the existing literature, pinning controllers for synchronization of drive-response systems were designed based on information of all nodes, but in some specific situations, the control gains may be very large and challenging to realize in practice. To overcome this problem, a novel pinning control policy is developed to achieve synchronization of delayed MNNs, which depends only on local information of MNNs, for reducing communication and calculation burdens. Furthermore, sufficient conditions for synchronization of delayed MNNs are provided. Finally, numerical simulation and comparative experiments are conducted to verify the effectiveness and superiority of the proposed pinning control method.

Identification of a new five-gene risk score for risk stratification and prognosis prediction in HCC.

Approximately 80% of primary liver cancer (PLC) is hepatocellular carcinoma (HCC), and the prognosis of HCC patients is unfavorable. Further studies are required to develop new prognostic tools for predicting the HCC patients' prognosis. The univariate Cox and LASSO regression were utilized to develop the multi-gene risk score. Single-sample Gene Set Enrichment Analysis (ssGSEA) was employed to assess differences of immune functions and cells. The model performance was evaluated by calibration curve and receiver operating characteristic curve (ROC). And qRT-PCR was utilized to evaluate the genes expression in clinical samples. Finally, a novel five-gene (KIF20A, CENPA, HMMR, G6PD, and ADH4) risk score was developed. Based on the median value of patients' risk scores, patients were divided into two groups: high-risk group and low-risk group. The Overall survival (OS) of patients in high-risk group was obviously poorer than that in the low-risk group. And the five-gene risk score was an independent risk factor correlated with patients' OS. Besides, a nomogram consisting of TNM stage and risk score was established. The results of decision curve, calibration curve, and ROC presented that the prognostic risk score and the nomogram had great predictive capability. Besides, ADH4's mRNA was reduced in HCC tissues, while the mRNA of KIF20A, CENPA, HMMR, and G6PD were overexpressed in HCC tissues. We developed a novel five-gene risk score that could predict HCC patients' prognosis. And these five genes could be promising therapeutic targets for HCC. The five-gene risk score and nomogram may be useful prognostic tools for HCC.

Intraoperative CT-assisted sacroiliac screws fixation for the treatment of posterior pelvic ring injury: a comparative study with conventional intraoperative imaging.

Pelvic injuries refer to the disruption of the inherent structural and mechanical integrity of the pelvic ring. Sacroiliac screw fixation technique is often applied for the treatment of posterior pelvic ring injury, which is prone to the iatrogenic injury. This study will compare the intraoperative and postoperative variables of patients underwent sacroiliac screw fixation with intraoperative CT and conventional imaging to evaluate the effect. Thirty-two patients with posterior pelvic ring injury treated by sacroiliac screw fixation from January 2019 to December 2020 were enrolled in this retrospective study. All patients were divided into two groups according to the different assistance of intraoperative imaging. Subsequently, the correlative data were compared and analysed statistically. Twelves cases were assigned to intraoperative CT group, and the remaining twenty cases were assigned to conventional group. There was no significant difference in duration of surgery, fracture healing time, time to ambulation, complications, and Matta radiological score. There was statistically significant difference (p < 0.05) in sacroiliac screws insertion time, length of incision, intraoperative blood loss, quality of screws position, and adjusted Majeed functional score, especially in the sexual intercourse part. With the assistance of intraoperative CT, a less misposition and functional impairment could be achieved, and a more satisfactory curative effect could be developed. Sacroiliac screws fixation with intraoperative CT is a more accurate and ideal method to treat posterior pelvic ring injuries.

Sacroiliac screws fixation navigated with three-dimensional printing personalized guide template for the treatment of posterior pelvic ring injury: A case report.

Objective: Pelvic injuries refer to the disruption of the inherent structural and mechanical integrity of the pelvic ring. Sacroiliac screw fixation technique is often used for the treatment of posterior pelvic ring injury, which is prone to the iatrogenic injury. Various attempts were proposed to avoid iatrogenic injuries, while the executing processes are usually too cumbersome. The patient-personalized guide template based on 3D printing technology has been considered as a promising method, which can achieve lower deviation and higher accuracy in a simple and convenient way. We reported the first case of posterior pelvic ring injury using 3D printing personalized guide template with the verification of intraoperative CT. Methods: The subject was a 74-year-old female with posterior pelvic ring injury. Two patient-specific guide templates were customized based on 3D printing technology, one for S1 and the other for S2. We used the guide templates for navigation to place the sacroiliac screws. The placement of screws was verified by intraoperative CT. Intraoperative and postoperative variables were collected. Results: The technique helped us successfully insert the sacroiliac screws into the safe zone. The intraoperative blood loss was 23.03 ml, and the duration of operation was 62 min. The exposure dose during CT scanning was 7.025 mSv. The assessment of screws position was excellent. Furthermore, there was no sign of any functional impairment postoperatively. Conclusion: Sacroiliac screws fixation with the assistance of 3D printing personalized guide template under the verification of intraoperative CT may be a promising method to treat posterior pelvic ring injuries.

Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles.

BACKGROUND: Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment. METHODS: Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein-protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis. RESULTS: In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2. CONCLUSIONS: This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.

Continuous-Time Time-Varying Policy Iteration.

A novel policy iteration algorithm, called the continuous-time time-varying (CTTV) policy iteration algorithm, is presented in this paper to obtain the optimal control laws for infinite horizon CTTV nonlinear systems. The adaptive dynamic programming (ADP) technique is utilized to obtain the iterative control laws for the optimization of the performance index function. The properties of the CTTV policy iteration algorithm are analyzed. Monotonicity, convergence, and optimality of the iterative value function have been analyzed, and the iterative value function can be proven to monotonically converge to the optimal solution of the Hamilton-Jacobi-Bellman (HJB) equation. Furthermore, the iterative control law is guaranteed to be admissible to stabilize the nonlinear systems. In the implementation of the presented CTTV policy algorithm, the approximate iterative control laws and iterative value function are obtained by neural networks. Finally, the numerical results are given to verify the effectiveness of the presented method.