Nanoparticles integrated with mild photothermal therapy and oxaliplatin for tumor chemotherapy and immunotherapy.

Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.

Correlation analysis of bone marrow microvessel density and miRNA expression on drug resistance in patients with chronic myelogenous leukemia after tyrosine kinase inhibitor treatment.

OBJECTIVE: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment. METHODS: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment. RESULTS: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance. CONCLUSION: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.

Effects of stereotactic body radiotherapy for clinical outcomes of patients with liver metastasis and hepatocellular carcinoma: A retrospective study.

This retrospective clinical study described the treatment efficacy and safety of stereotactic body radiotherapy (SBRT) for patients of hepatocellular carcinoma (HCC) and liver metastasis tumors. The therapeutic effect and prognosis of patients with liver cancer treated with stereotactic body radiation therapy (SBRT) at the Fudan University Shanghai Cancer Center (Shanghai, China) between July 2011 and December 2020 were retrospectively analyzed. Overall survival (OS), local control (LC) rates and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and the log-rank test. Local progression was defined as tumor growth after SBRT on dynamic computed tomography follow-up. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4. A total of 36 patients with liver cancer were enrolled in the present study. The prescribed dosages (14 Gy in 3 fractions or 16 Gy in 3 fractions) were applied for SBRT treatments. The median follow-up time was 21.4 months. The median OS time was 20.4 [95% confidence interval (CI): 6.6-34.2] months, and the 2-year OS rates for the total population, HCC group and liver metastasis group were 47.5, 73.3 and 34.2%, respectively. The median PFS time was 17.3 (95% CI: 11.8-22.8) months and the 2-year PFS rates for the total population, HCC group and liver metastasis group were 36.3, 44.0 and 31.4%, respectively. The 2-year LC rates for the total population, HCC group and liver metastasis group were 83.4, 85.7 and 81.6%, respectively. The most common grade IV toxicity for the HCC group was liver function impairment (15.4%), followed by thrombocytopenia (7.7%). There were no grade III/IV radiation pneumonia or digestive discomfort. The present study aimed to explore a safe, effective and non-invasive treatment method for liver tumors. At the same time, the innovation of the present study is to find a safe and effective prescription dose of SBRT in the absence of consensus on guidelines.

A pan-cancer analysis of the expression and molecular mechanism of DHX9 in human cancers.

Finding new targets is necessary for understanding tumorigenesis and developing cancer therapeutics. DExH-box helicase 9 (DHX9) plays a central role in many cellular processes but its expression pattern and prognostic value in most types of cancer remain unclear. In this study, we extracted pan-cancer data from TCGA and GEO databases to explore the prognostic and immunological role of DHX9. The expression levels of DHX9 were then verified in tumor specimens by western blot and immunohistochemistry (IHC). The oncogenic roles of DHX9 in cancers were further verified by in vitro experiments. We first verified that DHX9 is highly expressed in most tumors but significantly decreased in kidney and thyroid cancers, and it is prominently correlated with the prognosis of patients with different tumors. The phosphorylation level of DHX9 was also increased in cancers. Enrichment analysis revealed that DHX9 was involved in Spliceosome, RNA transport and mRNA surveillance pathway. Furthermore, DHX9 expression exhibited strong correlations with immune cell infiltration, immune checkpoint genes, and tumor mutational burden (TMB)/microsatellite instability (MSI). In liver, lung, breast and renal cancer cells, the knockdown or depletion of DHX9 significantly affected the proliferation, metastasis and EMT process of cancer cells. In summary, this pan-cancer investigation provides a comprehensive understanding of the prognostic and immunological role of DHX9 in human cancers, and experiments indicated that DHX9 was a potential target for cancer treatment.

Effects of Dezocine on the Reduction of Emergence Delirium after Laparoscopic Surgery: A Retrospective Propensity Score-Matched Cohort Study.

In China, dezocine is commonly employed as a partial agonist of mu/kappa opioid receptors during anesthesia induction for surgical patients, yet evidence supporting its causal association with emergence delirium is limited. The objective of this investigation was to evaluate the impact of intravenous dezocine administered during anesthesia induction on emergence delirium. The retrospective studied existing data containing medical records of patients undergoing an elective laparoscopy procedure and the study was conducted with ethics-board approval. The primary outcome was the incidence of emergence delirium. Secondary outcomes included the VAS in the PACU and 24 h after surgery, the RASS score in the PACU, postoperative MMSE, hospital stay, and ICU stay. A total of 681 patients were analyzed, after being propensity score-matched, the dezocine and non-dezocine group each had 245 patients. Emergence delirium occurred in 26/245 (10.6%) of patients who received dezocine and 41/245 (16.7%) of patients did not receive dezocine. Patients on whom dezocine was used were associated with a significantly lower incidence of emergence delirium (absolute risk difference, -6.1%, 95% CI, -12% to -0.2%; relative risk [RR], 0.63; 95% CI, 0.18-0.74). All secondary outcome measures and adverse outcomes were not significantly different. The use of dezocine during anesthesia induction was associated with a decreased incidence of emergence delirium after elective laparoscopic surgeries.

Chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma: A retrospective analysis.

PURPOSE: This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC treated with paclitaxel-liposome-based chemoradiotherapy between 2016 and 2019 were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis. RESULTS: Thirty-nine patients with locally advanced ESCC were included in this study. The median follow-up time was 31.5 months. The median OS time was 38.3 (95% confidence interval [CI]: 32.1-45.1) months, and the 1-, 2-, and 3-year OS rates were 84.6%, 64.1%, and 56.2%, respectively. The median PFS time was 32.1 (95% CI: 25.4-39.0) months, and the 1-, 2-, and 3-year PFS rates were 71.8%, 43.6%, and 43.6%, respectively. The most common Grade IV toxicity was neutropenia (30.8%) followed by lymphopenia (20.5%). There were no cases of Grade III/IV radiation pneumonia, and four patients (10.3%) had Grade III/IV esophagitis. CONCLUSION: Chemoradiotherapy using paclitaxel liposome and cisplatin is a well-tolerated and effective treatment regimen for locally advanced ESCC.

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era.

BACKGROUND: We investigated the role of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) according to tumor response in the magnetic resonance imaging (MRI) era. METHODS: We retrospectively evaluated patients with LS-SCLC without brain metastases (BMs) on MRI who achieved either complete response (CR) or partial response (PR) after initial chemoradiotherapy at our center from 2006 to 2017. RESULTS: This study comprised 116 patients (median age, 58 years; men, 92; women, 24). After initial chemoradiotherapy, 53 patients achieved CR, while 63 patients achieved PR. Eighty-three patients received PCI. Patients who received PCI had better overall survival (OS, 5-year: 52.5% vs. 35.1%; p = 0.012) and progression-free survival (PFS, 5-year: 45.0% vs. 28.2%; p = 0.001) and a lower incidence of BMs (5-year: 18.3% vs. 39.4%; p = 0.010). In the subgroup analysis, PCI improved OS (5-year: 67.8% vs. 46.7%, p = 0.005) and PFS (5-year: 65.2% vs. 35.0%, p = 0.021) and decreased BM risk (5-year: 12.1% vs. 52.4%, p = 0.002) for patients with CR. However, PCI had no benefit (5-year OS: 40.5% vs. 35.6%, p = 0.763; 5-year BMs: 24.6% vs. 31.9%, p = 0.561) for patients with PR. CONCLUSIONS: Tumor response remained an important factor for selecting patients for PCI in the MRI era. PCI should be recommended for patients with LS-SCLC who achieve CR after initial thoracic chemoradiotherapy.

Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Recent Advances in DNA Vaccines against Lung Cancer: A Mini Review.

Lung cancer is regarded as the major causes of patient death around the world. Although the novel tumor immunotherapy has made great progress in the past decades, such as utilizing immune checkpoint inhibitors or oncolytic viruses, the overall 5-year survival of patients with lung cancers is still low. Thus, development of effective vaccines to treat lung cancer is urgently required. In this regard, DNA vaccines are now considered as a promising immunotherapy strategy to activate the host immune system against lung cancer. DNA vaccines are able to induce both effective humoral and cellular immune responses, and they possess several potential advantages such as greater stability, higher safety, and being easier to manufacture compared to conventional vaccination. In the present review, we provide a global overview of the mechanism of cancer DNA vaccines and summarize the innovative neoantigens, delivery platforms, and adjuvants in lung cancer that have been investigated or approved. Importantly, we highlight the recent advance of clinical studies in the field of lung cancer DNA vaccine, focusing on their safety and efficacy, which might accelerate the personalized design of DNA vaccine against lung cancer.

Exercise Facilitates the M1-to-M2 Polarization of Microglia by Enhancing Autophagy via the BDNF/AKT/mTOR Pathway in Neuropathic Pain.

BACKGROUND: In neuropathic pain following peripheral nerve injury, microglia are rapidly activated and accumulated in the spinal cord. Physical exercise can alleviate neuropathic pain. However, the exact mechanism underlying this analgesic effect is not fully understood. OBJECTIVES: We aimed to investigate the molecular mechanisms by which exercise alleviates neuropathic pain in relation to brain-derived neurotrophic factor (BDNF), microglia polarization, and autophagy. STUDY DESIGN: A randomized controlled animal study divided into 2 stages. The first stage comprised 4 groups each with 6 mice, and the second stage comprised 6 groups, 3 with 18 mice and 3 with 12 mice. SETTING: Department of Anesthesiology, Lanzhou University Second Hospital, Orthopaedics Key Laboratory of Gansu Province, Lanzhou University. METHODS: Von Frey filaments, Western blotting, immunofluorescence, and transmission electron microscopy analyses were conducted to detect relevant markers. RESULTS: After peripheral nerve injury, exercise training downregulated BDNF expression and reversed microglial activation, as indicated by the increased expression of the M2 marker CD206 and decreased expression of the M1 marker CD86 in the spinal dorsal horn of mice. Autophagy flux was enhanced after exercise training, as suggested by the increased expression of the autophagy markers LC3-II/LC3-I and Beclin1 and decreased expression of the autophagy adaptor protein p62. Furthermore, autophagy inhibition by 3-methyladenine aggravated M1 polarization and hyperalgesia, whereas autophagy induced by rapamycin promoted M2 polarization and reduced hyperalgesia. Intrathecal injection of BDNF significantly upregulated BDNF expression, inhibited autophagy, triggered M1 polarization of spinal microglia, and aggravated hyperalgesia. Furthermore, BDNF regulated autophagy through the AKT/mTOR pathway, thereby participating in exercise training-mediated polarization of microglia after nerve injury. LIMITATIONS: The effect of exercise on autophagy and pain cannot be assessed in an in vitro model. The influence of intrathecal injection of BDNF on the metabolic changes in other neuronal cells and the subsequent effects on pain should be investigated. Further studies on how exercise training modulates microglial autophagy to alleviate neuropathic pain are needed. CONCLUSIONS: Exercise training promoted the recovery of sciatic nerve injury in mice, possibly by regulating microglial polarization through BDNF/AKT/mTOR signaling-mediated autophagy flux. We confirmed the efficacy of exercise training in alleviating neuropathic pain and suggest a new therapeutic target for neuropathic pain.

Review of phytomedicine, phytochemistry, ethnopharmacology, toxicology, and pharmacological activities of Cymbopogon genus.

The Cymbopogon genus belongs to the Andropoganeae family of the family Poaceae, which is famous for its high essential oil concentration. Cymbopogon possesses a diverse set of characteristics that supports its applications in cosmetic, pharmaceuticals and phytotherapy. The purpose of this review is to summarize and connect the evidence supporting the use of phytotherapy, phytomedicine, phytochemistry, ethnopharmacology, toxicology, pharmacological activities, and quality control of the Cymbopogon species and their extracts. To ensure the successful completion of this review, data and studies relating to this review were strategically searched and obtained from scientific databases like PubMed, Google Scholar, ResearchGate, ScienceDirect, and Elsevier. Approximately 120 acceptable reviews, original research articles, and other observational studies were included and incorporated for further analysis. Studies showed that the genus Cymbopogon mainly contained flavonoids and phenolic compounds, which were the pivotal pharmacological active ingredients. When combined with the complex ß-cyclodextrin, phytochemicals such as citronellal have been shown to have their own mechanism of action in inhibiting the descending pain pathway. Another mechanism of action described in this review is that of geraniol and citral phytochemicals, which have rose and lemon-like scents and can be exploited in soaps, detergents, mouthwash, cosmetics, and other products. Many other pharmacological effects, such as anti-protozoal, anti-bacterial, anti-inflammatory and anti-cancer have been discussed sequentially, along with how and which phytochemicals are responsible for the observed effect. Cymbopogon species have proven to be extremely valuable, with many applications. Its phytotherapy is proven to be due to its rich phytochemicals, obtained from different parts of the plant like leaves, roots, aerial parts, rhizomes, and even its essential oils. For herbs of Cymbopogon genus as a characteristic plant therapy, significant research is required to ensure their efficacy and safety for a variety of ailments.

Piezo1-mediated fluid shear stress promotes OPG and inhibits RANKL via NOTCH3 in MLO-Y4 osteocytes.

Piezo1, a mechanosensitive ion channel, participates in a variety of biological processes in maintaining bone homeostasis. As the most abundant cells in bones of the mammals, osteocytes play an essential role in bone formation, remodeling, and bone mass maintenance. Here, by exposing MLO-Y4 osteocytes to the fluid shear stress (FSS) microenvironment, we explored the effect of Piezo1-mediated FSS on the expression of the molecules critical to the process of bone formation and resorption, Receptor Activator of Nuclear Factor-Kappa-B Ligand (RANKL) and Osteoprotegerin (OPG). It was found that 9 dyne/cm2 loading for 30 minutes showed an upregulation trend on Piezo1 when MLO-Y4 osteocytes were exposed to an FSS microenvironment. FSS promotes the expression of OPG and inhibits the expression of RANKL. The blocker of Piezo1, GsMTx4, downregulates the effect of FSS on the expression of these two molecules. In addition, NOTCH3 was involved in this process. Thus, the results demonstrated that Piezo1-mediated FSS promotes the expression of OPG and inhibits the expression of RANKL via NOTCH3 in MLO-Y4 osteocytes.

Small molecules facilitate single factor-mediated sweat gland cell reprogramming.

BACKGROUND: Large skin defects severely disrupt the overall skin structure and can irreversibly damage sweat glands (SG), thus impairing the skin's physiological function. This study aims to develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages, which may provide a promising method to obtain desirable cell types for the functional repair and regeneration of damaged skin. METHODS: The expression of the SG markers cytokeratin 5 (CK5), cytokeratin 10 (CK10), cytokeratin 18 (CK18), carcino-embryonic antigen (CEA), aquaporin 5 (AQP5) and α-smooth muscle actin (α-SMA) was assessed with quantitative PCR (qPCR), immunofluorescence and flow cytometry. Calcium activity analysis was conducted to test the function of induced SG-like cells (iSGCs). Mouse xenograft models were also used to evaluate the in vivo regeneration of iSGCs. BALB/c nude mice were randomly divided into a normal group, SGM treatment group and iSGC transplantation group. Immunocytochemical analyses and starch-iodine sweat tests were used to confirm the in vivo regeneration of iSGCs. RESULTS: EDA overexpression drove HDF conversion into iSGCs in SG culture medium (SGM). qPCR indicated significantly increased mRNA levels of the SG markers CK5, CK18 and CEA in iSGCs, and flow cytometry data demonstrated (4.18 ± 0.04)% of iSGCs were CK5 positive and (4.36 ± 0.25)% of iSGCs were CK18 positive. The addition of chemical cocktails greatly accelerated the SG fate program. qPCR results revealed significantly increased mRNA expression of CK5, CK18 and CEA in iSGCs, as well as activation of the duct marker CK10 and luminal functional marker AQP5. Flow cytometry indicated, after the treatment of chemical cocktails, (23.05 ± 2.49)% of iSGCs expressed CK5+ and (55.79 ± 3.18)% of iSGCs expressed CK18+, respectively. Calcium activity analysis indicated that the reactivity of iSGCs to acetylcholine was close to that of primary SG cells [(60.79 ± 7.71)% vs. (70.59 ± 0.34)%, ns]. In vivo transplantation experiments showed approximately (5.2 ± 1.1)% of the mice were sweat test positive, and the histological analysis results indicated that regenerated SG structures were present in iSGCs-treated mice. CONCLUSION: We developed a SG reprogramming strategy to generate functional iSGCs from HDFs by using the single factor EDA in combination with SGM and small molecules. The generation of iSGCs has important implications for future in situ skin regeneration with SG restoration.

An increased posterior tibial slope is associated with a higher risk of graft failure following ACL reconstruction: a systematic review.

PURPOSE: The posterior tibial slope (PTS) is considered a risk factor for anterior cruciate ligament (ACL) injury. However, the influence of PTS on graft failure following ACL reconstruction remains relatively unknown. Therefore, this systematic review was conducted to investigate whether PTS could be a potential risk factor for graft failure after ACL reconstruction. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, and Wanfang Database were comprehensively searched from inception to March 31, 2021. Observational studies reporting the associations of medial tibial plateau slope (MTPS) or lateral tibial plateau slope (LTPS) with graft failure after ACL reconstruction were evaluated. RESULTS: Twenty studies involving 12 case-control studies, 4 retrospective studies and 4 cross-sectional studies including 5326 patients met the final inclusion criteria. The high heterogeneity and the characteristics of nonrandomized controlled trials limited data synthesis. Fifteen of the 20 included studies detected a significant association between increased PTS and ACL graft failure, while 5 studies concluded that increased PTS was not associated with ACL graft failure. Ten studies suggested that MTPS is associated with ACL graft failure, and six studies suggested that LTPS is associated with ACL graft failure. The mean MTPS values for nonfailure group ranged from 3.5° ± 2.5° to 14.4° ± 2.8°. For the graft failure group, MTPS ranged from 4.71° ± 2.41° to 17.2° ± 2.2°. The mean LTPS values for nonfailure group ranged from 2.9° ± 2.1° to 11.9° ± 3.0°. For the graft failure group, LTPS ranged from 5.5° ± 3.0° to 13.3° ± 3.0°. The reported PTS values that caused ACL graft failure was greater than 7.4° to 17°. CONCLUSION: Based on the current clinical evidence, increased PTS is associated with a higher risk of ACL graft failure after ACL reconstruction. Despite various methods of measuring PTS have high reliability, there is still vast disagreement in the actual value of PTS. LEVEL OF EVIDENCE: IV.

Development and validation of a novel screening tool for osteoporosis in older US adults: The NHANES cross-sectional study.

PURPOSE: Osteoporosis (OP) is a common disease among adults aged >50 years. At present, the main approach to screen or to diagnosis OP is mainly via bone mineral density (BMD) testing, which might not be optimal for OP screening. This study aimed to develop and validate a convenient and effective prediction model for screening OP based on the demographic information, medical history, and lifestyle habits in the elderly in the United States. METHODS: All data were collected from the National Health and Nutrition Survey database. Participants aged ≥50 years with complete BMD data were included in this study. Twelve candidate predictors were initially selected to develop the prediction model. Final predictors screening and model development were based on multivariate logistic regression. Model discrimination (C statistic) and calibration (Brier scores) were calculated to evaluate the performance of the model. Internal validation was performed using the bootstrap resampling technique, and external validation was based on the validation cohort. RESULTS: The screening tool was developed with individual patient data from 1941 patients and validated with data from 1947 patients after the development of the model. Seven predictors (patient age, sex, race, body mass index, physical activity, sleep duration, and history of fracture) were included in the final prediction model, and the final model had a C statistic of 0.849 [95% confidence interval (CI): 0.820-0.878] and Brier scores of 0.062 [95% CI: 0.054-0.070] on the development cohort. For the validation of the developed model, the results showed a C statistic >0.800 and Brier scores <0.070, irrespective of internal validation or external validation. CONCLUSIONS: A novel screening tool for OP in the elderly, which has excellent discrimination and useful calibration, has been developed and externally validated. Considering its simplicity, generalizability, and accuracy, this tool has the potential to become a practical mean for the elderly to screen OP.

Lycium barbarum Polysaccharides Promotes Mitochondrial Biogenesis and Energy Balance in a NAFLD Cell Model.

OBJECTIVE: To explore the protective effect and underlying mechanism of Lycium barbarum polysaccharides (LBP) in a non-alcoholic fatty liver disease (NAFLD) cell model. METHODS: Normal human hepatocyte LO2 cells were treated with 1 mmol/L free fatty acids (FFA) mixture for 24 h to induce NAFLD cell model. Cells were divided into 5 groups, including control, model, low-, medium- and high dose LBP (30,100 and 300 µg/mL) groups. The monosaccharide components of LBP were analyzed with high performance liquid chromatography. Effects of LBP on cell viability and intracellular lipid accumulation were assessed by cell counting Kit-8 assay and oil red O staining, respectively. Triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), adenosine triphosphate (ATP) and oxidative stress indicators were evaluated. Energy balance and mitochondrial biogenesis related mRNA and proteins were determined by quantitative real-time polymerase chain reaction and Western blot, respectively. RESULTS: Heteropolysaccharides with mannose and glucose are the main components of LBP. LBP treatment significantly decreased intracellular lipid accumulation as well as TG, ALT, AST and malondialdehyde levels (P<0.05 or P<0.01), increased the levels of superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, and ATP in NAFLD cell model (P<0.05). Meanwhile, the expression of uncoupling protein 2 was down-regulated and peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A pathway was up-regulated (P<0.05). CONCLUSION: LBP promotes mitochondrial biogenesis and improves energy balance in NAFLD cell model.

Diagnostic Value of Next-Generation Sequencing in Periprosthetic Joint Infection: A Systematic Review.

Next-generation sequencing (NGS) has developed rapidly in the last decade and is emerging as a promising diagnostic tool for periprosthetic joint infection (PJI). However, its diagnostic value for PJI is still uncertain. This systematic review aimed to explore the diagnostic value of NGS for PJI and verify its accuracy for culture-negative PJI patients. We conducted this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Medline, Embase, and Cochrane Library were searched to identify diagnostic technique studies evaluating the accuracy of NGS in the diagnosis of PJI. The diagnostic sensitivity, specificity, and positive and negative predictive values were estimated for each article. The detection rate of NGS for culture-negative PJI patients or PJI patients with antibiotic administration history was also calculated. Of the 87 identified citations, nine studies met the inclusion criteria. The diagnostic sensitivities and specificities of NGS ranged from 63% to 96% and 73% to 100%, respectively. The positive and negative predictive values ranged from 71% to 100% and 74% to 95%, respectively. The detection rate of NGS for culture-negative PJI patients in six studies was higher than 50% (range from 82% to 100%), while in three studies it was lower than 50% (range from 9% to 31%). Also, the detection rate of NGS for PJIs with antibiotic administration history ranged from 74.05% to 92.31%. In conclusion, this systematic review suggests that NGS may have the potential to be a new tool for the diagnosis of PJI and should be considered to be added to the portfolio of diagnostic procedures. Furthermore, NGS showed a favorable diagnostic accuracy for culture-negative PJI patients or PJI patients with antibiotic administration history. However, due to the small sample sizes of studies and substantial heterogeneity among the included studies, more research is needed to confirm or disprove these findings.

Modeling the Solubility of Sulfur in Sour Gas Mixtures Using Improved Support Vector Machine Methods.

The study of sulfur solubility is of great significance to the safe development of sulfur-containing gas reservoirs. However, due to measurement difficulties, experimental research data on sulfur solubility thus far are limited. Under the research background of small samples and poor information, a weighted least-squares support vector machine (WLSSVM)-based machine learning model suitable for a wide temperature and pressure range is proposed to improve the prediction accuracy of sulfur solubility in sour gas. First, we use the comprehensive gray relational analysis method to extract important factors affecting sulfur solubility as the model input parameters. Then, we use the whale optimization algorithm (WOA) and gray wolf optimizer (GWO) intelligence algorithms to find the optimal solution of the penalty factor and kernel coefficient and bring them into three common kernel functions. The optimal kernel function is calculated, and the final WOA-WLSSVM and GWO-WLSSVM models are established. Finally, four evaluation indicators and an outlier diagnostic method are introduced to test the proposed model's performance. The empirical results show that the WOA-WLSSVM model has better performance and reliability; the average absolute relative deviation is as low as 3.45%, determination coefficient (R 2) is as high as 0.9987, and the prediction accuracy is much higher than that of other models.

PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer.

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

CT Radiomics for the Prediction of Synchronous Distant Metastasis in Clear Cell Renal Cell Carcinoma.

PURPOSE: The aim of this study was to construct and verify a computed tomography (CT) radiomics model for preoperative prediction of synchronous distant metastasis (SDM) in clear cell renal cell carcinoma (ccRCC) patients. METHODS: Overall, 172 patients with ccRCC were enrolled in the present research. Contrast-enhanced CT images were manually sketched, and 2994 quantitative radiomic features were extracted. The radiomic features were then normalized and subjected to hypothesis testing. Least absolute shrinkage and selection operator (LASSO) was applied to dimension reduction, feature selection, and model construction. The performance of the predictive model was validated through analysis of the receiver operating characteristic curve. Multivariate and subgroup analyses were performed to verify the radiomic score as an independent predictor of SDM. RESULTS: The patients randomized into a training (n = 104) and a validation (n = 68) cohort in a 6:4 ratio. Through dimension reduction using LASSO regression, 9 radiomic features were used for the construction of the SDM prediction model. The model yielded moderate performance in both the training (area under the curve, 0.89; 95% confidence interval, 0.81-0.97) and the validation cohort (area under the curve, 0.83; 95% confidence interval, 0.69-0.95). Multivariate analysis showed that the CT radiomic signature was an independent risk factor for clinical parameters of ccRCC. Subgroup analysis revealed a significant connection between the SDM and radiomic signature, except for the lower pole of the kidney subgroup. CONCLUSIONS: The CT-based radiomics model could be used as a noninvasive, personalized approach for SDM prediction in patients with ccRCC.