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Hong-Tao Jiang, Wei Li, Biao Zhang, Qiang Gong, Hai-Ling Qie Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of ChinaCorrespondence: Hai-Ling Qie; Qiang GongDepartment of Thoracic Surgery, Affiliated Hospital of Hebei University, No. 212, Yu-Hua East Road, Lian-Chi District, Baoding, 071000, People’s Republic of ChinaTel +86 15930757546; +86 18903363263Email qiehailing@163.com; 5751564@qq.comPurpose: The present study was to investigate the real-world efficacy and safety of anlotinib monotherapy as third-line therapy for elderly patients with advanced non-small cell lung cancer (NSCLC).Methods: A total of 83 elderly patients (> 65 years) with NSCLC who were progressed at least two lines of previous systemic therapy were recruited retrospectively. Patients were treated with anlotinib monotherapy (12 mg or 10 mg). Efficacy of anlotinib was assessed and all the patients were followed up regularly. Adverse reactions were collected during anlotinib administration. Univariate analysis was performed using Log rank test and multivariate analysis was adjusted by Cox regression analysis. Additionally, prognostic analysis according to common adverse reactions was implemented to identify the potential clinical significance.Results: The best overall response of the 83 elderly patients during anlotinib monotherapy indicated that partial response (PR) was observed in six patients, stable disease (SD) was noted in 59 patients, and progressive disease (PD) was reported in 18 patients. Consequently, the objective response rate (ORR) was 7.2% (95% CI=2.7– 15.1%) and the disease control rate (DCR) was 78.3% (95% CI=67.9– 86.6%). The median progression-free survival (PFS) of the 83 elderly patients with NSCLC was 4.2 months (95% CI=3.51– 4.89). Furthermore, the median overall survival (OS) of the 83 patients was 9.6 months (95% CI=6.65– 12.55). The safety profile suggested that the relatively common adverse reactions of the elderly patients with ES-SCLC receiving anlotinib therapy were hypertension (49.4%), fatigue (45.8%), and hand–foot syndrome (39.8%). Interestingly, association analysis exhibited that the median PFS of patients with hypertension and non-hypertension was 4.5 and 3.0 months, respectively (χ2=6.306, P=0.012).Conclusion: Anlotinib monotherapy demonstrated a satisfactory efficacy and tolerable safety profile in third-line settings for elderly patients with advanced NSCLC. Patients who experienced a hypertension adverse reaction induced by anlotinib therapy might confer superior PFS. The conclusion should be validated in prospective clinical trials subsequently.Keywords: elderly non-small cell lung cancer, anlotinib, efficacy, prognosis, safety, biomarker

Xin Zhou,1 Shou-Gen Cao,1 Xiao-Jie Tan,1 Xiao-Dong Liu,1 Ze-Qun Li,1 Ling-Xin Kong,2 Yu-Long Tian,1 Dan Liu,1 Shuai Shen,1 Yu-Qi Sun,1 Hai-Tao Jiang,1 Yan-Bing Zhou1 1Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Yan-Bing ZhouDepartment of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao City, Shandong Province, People’s Republic of ChinaTel +86-13708971773Email zhouyanbing999@aliyun.comPurpose: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy.Patients and Methods: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1– 3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms.Results: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1– 5 (average: 2.55± 0.21 vs 3.10± 0.42, P< 0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63± 16.74 vs 72.60± 20.92, P< 0.001) and defecation (72.20± 16.24 vs 95.78± 17.75, P< 0.001) were shorter; the frequency of nausea were fewer (1.88± 1.09 vs 2.58± 0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63± 0.63 vs 6.93± 0.69, P< 0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported.Conclusion: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.Keywords: stomach neoplasms, acupuncture therapy, enhanced recovery after surgery, pain management, gastrointestinal function

Mei-Xiang Yu,1,* Xiao-Qin Ma,1,* Xin Song,2 Yong-Mei Huang,3 Hui-Ting Jiang,1 Jing Wang,1 Wan-Hua Yang1,4 1Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 2South Campus, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201100, People’s Republic of China; 3Jinshan Hospital, Shanghai Fudan University School of Medicine, Shanghai 201508, People’s Republic of China; 4Department of Pharmacy, Ruijin Hospital North Affiliated to the Shanghai Jiao Tong University Medical School, Shanghai 201801, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wan-Hua Yang Email yangwanhuaxy@163.comBackground: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti–inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation.Methods: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword “(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ”, and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability.Results: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins.Conclusion: Our results confirmed the anti–inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.Keywords: Shenjin Huoxue Mixture, osteoarthritis, active ingredients, pharmacological mechanisms, network pharmacology, thin-layer chromatography

Objective: To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass.Methods: A total of 60 adult patients'spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile, the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15 cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed.Results: The diameter and length of S(1)-S(5) sacral pedicle and lateral mass screw trajectory were regular, with about 20 degree inclination angle. The S(1) pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P larger than 0.05). The entry points of S(2)-S(5) pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process. The lateral mass screw entry point of S(2)-S(5) was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P less than 0.05).Conclusion: Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx, but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca 2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression., (© 2024. The Author(s).)

Disulfidptosis was recently reported to be caused by abnormal disulfide accumulation in cells with high SLC7A11 levels subjected to glucose starvation, suggesting that targeting disulfidptosis was a potential strategy for cancer treatment. We analyzed the relationships between gene expression and mutations and prognoses of patients. In addition, the correlation between gene expression and immune cell infiltration was explored. The potential regulatory mechanisms of these genes were assessed by investigating their related signaling pathways involved in cancer, their expression patterns, and their cellular localization. Most cancer types showed a negative correlation between the gene-set variation analysis (GSVA) scores and infiltration of B cells and neutrophils, and a positive correlation between GSVA scores and infiltration of natural killer T and induced regulatory T cells. Single-cell analysis revealed that ACTB , DSTN , and MYL6 were highly expressed in different bladder urothelial carcinoma subtypes, but MYH10 showed a low expression. Immunofluorescence staining showed that actin cytoskeleton proteins were mainly localized in the actin filaments and plasma membrane. Notably, IQGAP1 was localized in the cell junctions. In conclusion, this study provided an overview of disulfidptosis-related actin cytoskeleton genes in pan-cancer. These genes were associated with the survival of patients and might be involved in cancer-related pathways., Competing Interests: Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Background: Diabetic foot ulcers (DFUs) have become a global health concern, which can lead to diabetic foot infection (DFI), lower leg amputation, and even mortality. Though the standard of care (SOC) practices have been recognized as the "gold standard" for DFU care, SOC alone may not be adequate to heal all DFUs and prevent their recurrence. The use of dermal matrix has emerged as an adjuvant treatment to enhance DFU healing. The current study aimed to evaluate the effectiveness and safety of dermal matrix application as an adjuvant treatment to the SOC., Methods: The databases of PubMed, Embase and CENTRAL were independently searched by two authors, with the following key terms: "diabetic foot ulcer", "acellular dermal matrix", "wound healing", and so on. Randomized controlled trials (RCTs) evaluated the efficacy and safety of dermal matrix in the treatment of DFUs were eligible for inclusion. The primary outcomes analyzed included time to complete healing and complete healing rate at the final follow-up, while secondary outcomes included wound area, ulcer recurrence rate, amputation risk and complication risk. Meta-analyses were performed using random-effect or fixed-effect models, based on the heterogeneity test., Results: This study included a total of 15 RCTs with a total of 1524 subjects. Of these, 689 patients were treated with SOC alone, while 835 patients received SOC plus dermal matrix. Compared to the SOC group, significantly shorter time (MD = 2.84, 95%CI: 1.37 ~ 4.32, p < 0.001***) was required to achieve complete healing in dermal matrix group. Significantly higher complete healing rate (OR = 0.40, 95%CI: 0.33 ~ 0.49, p < 0.001***) and lower overall (RR = 1.83, 95%CI: 1.15 ~ 2.93, p = 0.011*) and major (RR = 2.64, 95%CI: 1.30 ~ 5.36, p = 0.007**) amputation risks were achieved in dermal matrix group compared to SOC group. No significant difference was found in the wound area, ulcer recurrence rate, and complication risk between the two groups., Conclusions: The application of dermal matrix as an adjuvant therapy in conjunction with SOC effectively improved the healing process of DFUs and reduced the amputation risk when compared to SOC alone. Furthermore, dermal matrix application was well tolerated by the subjects with no added complication risk., (© 2024. The Author(s).)

Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Extracellular deposition of β-amyloid (Aβ) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer's disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aβ, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD.

Background: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1., Methods: ATRA content was detected with ELISA and HPLC-MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro-computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism., Results: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/β-catenin, and reduced by inhibiting this pathway. β-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1., Conclusions: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

Low back pain (LBP) is a prevalent health problem worldwide that affects over 80% of adults during their lifetime. Intervertebral disc degeneration (IDD) is a well-recognized leading cause of LBP. IDD is classified into five grades according to the Pfirrmann classification system. The purpose of this study was to identify potential biomarkers in different IDD grades through an integrated analysis of proteome sequencing (PRO-seq), bulk RNA sequencing (bRNA-seq) and single-cell RNA sequencing (scRNA-seq) data. Eight cases of grade I-IV IDD were obtained. Grades I and II were considered non-degenerative discs (relatively normal), whereas grades III and IV were considered degenerative discs. PRO-seq analysis was performed to identify differentially expressed proteins (DEPs) in various IDD grades. Variation analysis was performed on bRNA-seq data to differentiate expressed genes (DEGs) in normal and degenerated discs. In addition, scRNA-seq was performed to validate DEGs in degenerated and non-degenerated nucleus pulposus (NP). Machine learning (ML) algorithms were used to screen hub genes. The receiver operating characteristic (ROC) curve was used to validate the efficiency of the screened hub genes to predict IDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze function enrichment and signaling pathways. Protein-protein interaction (PPI) network was used to prioritize disease-related proteins. SERPINA1, ORM2, FGG and COL1A1 were identified through PRO-seq as the hub proteins involved in regulating IDD. ML algorithms selected ten hub genes, including IBSP, COL6A2, MMP2, SERPINA1, ACAN, FBLN7, LAMB2, TTLL7, COL9A3, and THBS4 in bRNA-seq. Since serine protease inhibitor clade A member 1 (SERPINA1) was the only common gene, its accuracy in degenerated and non-degenerated NP cells was validated using scRNA-seq. Then, the rat degeneration model of caudal vertebra was established. The expression of SERPINA1 and ORM2 was detected using immunohistochemical staining of human and rat intervertebral discs. The results showed that SERPINA1 was poorly expressed in the degenerative group. We further explored the potential function of SERPINA1 by Gene Set Enrichment Analysis (GSEA) and cell-cell communication. Therefore, SERPINA1 can be used as a biomarker to regulate or predict the progress of disc degeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Lu, Zhou, Jiang and Chu.)

Studies reported the positive and negative osteogenic effects of MEG3 in mesenchymal stem cells (MSCs). This study aims at clarifying the osteogenic potential of MEG3 and the underlying mechanism. Bone morphogenetic protein 9- (BMP9-) transfected MSCs were recruited as an osteogenic model in vitro , and ectopic bone formation were used in vivo to explore the effect of MEG3 on osteogenesis. We found that overexpression of MEG3 facilitated BMP9-induced osteogenic markers, ALP activities, and matrix mineralization. However, knockdown of MEG3 attenuated BMP9-induced osteogenic markers. MEG3 increased the phosphorylation of GSK-3 β and the protein level of β -catenin. Pyruvate dehydrogenase kinase 4 (PDK4) can also combine with GSK-3 β and increase the latter phosphorylation. Moreover, MEG3 increased the mRNA level of PDK4. The ceRNA analysis showed that MEG3 may regulate the expression of PDK4 via microRNA 532-5p (miR-532-5p). The MEG3-enhanced GSK-3 β / β -catenin axis can be attenuated by miR-532-5p, and miR-532-5p inhibitor partly rescued endogenous PDK4 and MEG3-mediated expression of PDK4. MEG3 may potentiate PDK4 and GSK-3 β / β -catenin by inhibiting miR-532-5p., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Yuan-Yuan Yang et al.)

Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways., Competing Interests: Competing interests The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

With the rapid development of endoscopic technology, fully endoscopic microvascular decompression (MVD) has been widely used in the treatment of hemifacial spasm (HFS), and has achieved good effect. The present study reviewed 5 cases of HFS treated by fully endoscopic MVD. After fully endoscopic MVD, the symptom of facial involuntary twitching was relieved in each of the 5 patients with an effective rate of 100%. Among the cases, 4 had no postoperative complications, such as cranial nerve dysfunction, and cerebellar or brainstem injury, while 1 patient had postoperative aseptic meningitis and recovered after follow-up treatment. In these 5 cases of MVD, endoscopy played an important role in identifying the offending blood vessels, which is of great significance to improve the surgical effect and safety. Furthermore, the postoperative effects showed that endoscopy has certain potential and advantages in MVD. Therefore, fully endoscopic MVD is also a feasible method for the treatment of HFS., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

What Is Known and Objective: Although osimertinib achieved convincing efficacy for patients with EGFR T790M-positive non-small-cell lung cancer (NSCLC) as second-line treatment in the AURA3 clinical trials, patients developed drug resistance ultimately. Therefore, the present study was to investigate the clinical outcome and safety of osimertinib plus anlotinib for patients with previously treated EGFR T790M-positive NSCLC., Methods: Designed as a retrospective study, this study consecutively included a total of 33 patients with advanced NSCLC who possessed a EGFR T790M-positive mutation and progressed after the first-line therapy. Eligible patients were treated with osimertinib plus anlotinib. Baseline characteristics of the patients were collected during hospitalization. Efficacy of the combination regimen was assessed with the change of target lesion using imaging evidence according to RECIST 1.1 criteria, and all the patients were followed up regularly. Adverse reactions were collected and documented during the treatment. Univariate analysis according to baseline characteristic subgroups was performed using log-rank test, and multivariate analysis was carried out by Cox regression analysis., Results and Discussion: The best overall response of the patients during osimertinib and anlotinib combination indicated that complete response was found in one patient, partial response was observed in 26 patients, stable disease was noted in 5 patients and progressive disease was reported in one patient. Therefore, objective response rate (ORR) of the combination regimen was 81.8% (95%CI: 64.5%-93.0%), and disease control rate (DCR) was 97.0% (95%CI: 84.2%-99.9%). Furthermore, the median progression-free survival (PFS) of the 33 patients with NSCLC was 15.5 months (95%CI: 6.19-24.81). In addition, the median overall survival (OS) of the 33 patients with NSCLC was 23.8 months (95% CI: 17.67-29.93). Safety profile suggested that the most common adverse reactions of the patients with NSCLC who received anlotinib plus osimertinib were hypertension (63.6%), fatigue (57.6%), diarrhoea (48.5%%), dermal toxicity (39.4%) and proteinuria (33.3%). Interestingly, multivariate Cox regression analysis for PFS demonstrated that ECOG performance status was an independent factor to predict the PFS of the combination regimen., What Is New and Conclusion: Osimertinib plus anlotinib regimen preliminarily exhibited encouraging clinical outcomes and acceptable safety profile for patients with previously treated EGFR T790M-positive NSCLC numerically. This conclusion should be validated in prospective clinical trials., (© 2022 John Wiley & Sons Ltd.)

Purpose: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis., Methods: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay., Results: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups., Conclusion: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis., Trial Registration Number: ChiCTR1800015417., (© 2022. The Author(s).)

Chitosan extracted from natural products has gained tremendous attention in the field of adsorption and separation due to its inherent biocompatibility and potential applications. In this research, we synthesized a new type of spherical chitosan adsorbent (SCA) by controlling the mass transfer rate of the entanglement of the polymer chains in the recombination process. This SCA is a highly crystalline polymer material with outstanding mechanical strength, high adsorption capacity, a porous surface and suitable particle size distribution. The value of the sphericity of attrition of this SCA was 89.8%, which is the same as that of the commercial macroporous resin with a polystyrene matrix. The X-ray diffraction (XRD) patterns and differential scanning calorimetry (DSC) curves showed a significant change from powder to spherical structure and confirmed that the SCA is highly ordered and crystalline. Optical microscopy (OM) and scanning electron microscopy (SEM) demonstrated that the SCA was composed of a tightly stacked fiber structure, indicating the homogeneity of the polymerization. The porous structure of the surface provided a channel for mass transfer, which was indicated by a test of the ion exchange capacity and the adsorption performance of the SCA with Cu(ii) as the adsorbed subject. The adsorption capacity was higher than those of all reported non-composite chitosan materials. Therefore, we have successfully synthesized a completely green, nontoxic and environmentally friendly adsorbing resin equipped with excellent mechanical properties and adsorption capacity for future applications in many new fields., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set( n =142)and a test set( n =62)at a ratio of 7∶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P <0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans( P =0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model( P =0.001 and P =0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted ( n =57) or laparoscopic-assisted right hemicolectomy ( n =231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ 2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t =-1.477, P =0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z =-4.591, P <0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t =4.491, P <0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation ( t : -2.888, -2.946, -2.328, all P <0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596, P =0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group ( P >0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC 50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Background: Acute kidney injury (AKI) was characterized by loss of renal function, associated with chronic kidney disease, end-stage renal disease, and length of hospital stay. Long non-coding RNAs (lncRNAs) participated in AKI development and progression. Here, we aimed to investigate the roles and mechanisms of lncRNA MALAT1 in AKI., Methods: AKI serum samples were obtained from 129 AKI patients. ROC analysis was conducted to confirm the diagnostic value of MALAT1 in differentiating AKI from healthy volunteers. After hypoxic treatment on HK-2 cells, the expressions of inflammatory cytokines, MALAT1, miR-204, APOL1, p65, and p-p65, were measured by RT-qPCR and Western blot assays. The targeted relationship between miR-204 and MALAT1 or miR-204 and APOL1 was determined by luciferase reporter assay and RNA pull-down analysis. After transfection, CCK-8, flow cytometry, and TUNEL staining assays were performed to evaluate the effects of MALAT1 and miR-204 on AKI progression., Results: From the results, lncRNA MALAT1 was strongly elevated in serum samples from AKI patients, with the high sensitivity and specificity concerning differentiating AKI patients from healthy controls. In vitro, we established the AKI cell model after hypoxic treatment. After experiencing hypoxia, we found significantly increased MALAT1, IL-1β, IL-6, and TNF-α expressions along with decreased miR-204 level. Moreover, the targeted relationship between MALAT1 and miR-204 was confirmed. Silencing of MALAT1 could reverse hypoxia-triggered promotion of HK-2 cell apoptosis. Meanwhile, the increase of IL-1β, IL-6, and TNF-α after hypoxia treatment could be repressed by MALAT1 knockdown as well. After co-transfection with MALAT1 silencing and miR-204 inhibition, we found that miR-204 could counteract the effects of MALAT1 on HK-2 cell progression and inflammation after under hypoxic conditions. Finally, NF-κB signaling was inactivated while APOL1 expression was increased in HK-2 cells after hypoxia treatment, and lncRNA MALAT1 inhibition reactivated NF-κB signaling while suppressed APOL1 expression by sponging miR-204., Conclusions: Collectively, these results illustrated that knockdown of lncRNA MALAT1 could ameliorate AKI progression and inflammation by targeting miR-204 through APOL1/NF-κB signaling., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Osteosarcoma (OS) is a lethal bone malignancy. Circular RNAs (circRNAs) have emerged as important regulators of OS development. CircRNA cyclin dependent kinase 14 (circ&#95;CDK14) was reported to be a potential oncogene in OS. However, the mechanistic pathway by which circ&#95;CDK14 functions in OS is largely unknown. The relative expression of circ&#95;CDK14, microRNA (miR)-520a-3p, and GRB2 Associated Binding Protein 1 (GAB1) was evaluated by quantitative real-time PCR and western blot assays. Flow cytometry was employed to monitor cell cycle distribution and apoptosis. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were performed to assess cell viability and colony formation ability, respectively. Western blot assay was also used to detect the expression of apoptosis-related proteins. Transwell assay was carried out to monitor cell migration and invasion. Additionally, the target association between miR-520a-3p and circ&#95;CDK14 or GAB1 was confirmed by a dual-luciferase reporter assay. Xenograft assay was applied to investigate the role of circ&#95;CDK14 in vivo. Circ&#95;CDK14 and GAB1 expression was upregulated, while miR-520a-3p was downregulated in OS tissues and cells. Circ&#95;CDK14 depletion hindered OS cell proliferation, metastasis, and tumorigenesis while facilitated apoptosis, which were all ameliorated by miR-520a-3p inhibition. Circ&#95;CDK14 could sponge miR-520a-3p. miR-520a-3p targeted GAB1 to repress OS cell proliferation and metastasis. Circ&#95;CDK14 knockdown blocked OS tumor growth in vivo. Circ&#95;CDK14 might positively affect OS development by modulating the miR-520a-3p/GAB1 axis.

Background: Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA)., Methods: Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein-DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis., Results: ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARβ) was elevated. RARβ inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARβ can regulate the expression of Serpina3n., Conclusion: ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.

Background: MicroRNAs were reported to be involved in the progression of intervertebral disc degeneration (IDD). This study focused on the potential prognostic value and the underlying mechanism of miR-182 in IDD., Methods: The expression level of miR-182 in plasma samples from 60 IDD patients and 60 healthy controls were examined in the present study. Then, the relationship between miR-182 expression and clinical features of IDD patients was analyzed. Moreover, the nucleus pulposus (NP) cells were cultured and transfected with either miR-182 inhibitor, mimics, or NC to explore the effects of miR-182 on cell proliferation and apoptosis. Furthermore, expression levels of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3 were also evaluated., Results: The expression level of miR-182 was dramatically increased in plasma samples of IDD patients compared with the controls. Moreover, ROC analysis indicated that miR-182 was a feasible diagnostic indicator for the diagnosis of IDD. According to the Japanese Orthopaedic Association (JOA) score, the prognosis of patients with the lower expression levels of miR-182 was better than for those with the higher expression levels of miR-182 in IDD. Furthermore, the miR-182 inhibitor significantly increased the proliferation, decreased the apoptosis of human NP cells, and altered the expression of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3. On the contrary, miR-182 mimics notably inhibited proliferation but promoted apoptosis of human NP cells and increased Bax and Caspase-3 expressions while reducing the Bcl-2 level., Conclusions: miR-182 was negatively correlated with the prognosis of the IDD patients and affected the proliferation and apoptosis of NP cells in vitro.

Kidney transplantation is the most effective treatment for end-stage renal disease, but is limited by the increasing shortage of deceased and living human donor kidneys. Xenotransplantation using pig organs provides the possibility to resolve the issue of organ supply shortage and is regarded as the next great medical revolution. In the past five years, there have been sequential advances toward the prolongation of life-supporting pig kidney xenograft survival in non-human primates, with the longest survival being 499 days. This progress is due to the growing availability of pigs with multi-layered genetic modifications to overcome the pathobiological barriers and the application of a costimulation blockade-based immunosuppressive regimen. These encouraging results bring the hope to initiate the clinical trials of pig kidney transplantation in the near future. In this review, we summarized the latest advances regarding pig kidney xenotransplantation in preclinical models to provide a basis for future investigation and potential clinical translation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although plant-plant interactions have been intensively studied, few studies examined sex-related neighbor interactions in dioecious plant species. Here, we investigated the sexual diffe-rences in biomass accumulation, and analyzed the sexual neighbor effects and yields of sexual combination in Populus cathayana seedlings under the treatments of inter- and intra-sex neighbors and soil sterilization. The results showed that biomass accumulation of P. cathayana decreased in both of sexes when grown with an intra-sex neighbor. Females increased biomass accumulation under non-sterilization condition when grown with an inter-sex neighbor. Soil sterilization decreased biomass accumulation in both sexes of these plants, especially for females. Soil sterilization treatments did not significantly affect intra-sex interactions, but neutralized the positive effects in females and led the effects in males to turn from neutral to negative in inter-sex neighbors. The highest biomass in female-male combination under non-sterilization condition and the lowest biomass in male-male combination under sterilization condition were observed among combinations. These results indicated that the growth of female and male P. cathayana differed in their responses to their sexual neighbors, and that such neighbor effects were affected by soil microorganism. Our results could contribute to improve the productivity of poplar plantations in silviculture.

With improvements in endoscopy and laser technology, flexible ureteroscopy (FURS) has been a viable treatment option for large renal stones. Here, we share our experience of the FURS treatment for renal stones 2 cm or greater.We evaluated 251 consecutive patients who underwent FURS and holmium laser lithotripsy for renal stones 2 cm or greater between January 2015 and April 2019. Stone size was defined as the longest axis on non-contrast computed tomography. Data were retrospectively collected from electronic medical records. Patient demographics, stone clearance rates and perioperative complications were evaluated.There were 165 male patients and 86 female patients with an average age of 46.9 years (range 22-80 years). Mean stone size was 2.7 cm and the average number of procedures was 1.4 (range 1-5). The stone-free rate at the end of the first, second and third procedure was 61.9%, 82.9%, and 89.5%, respectively. The final stone-free rate decreased as stone size grows, and it was only 58.3% for kidney stones larger than 4 cm after an average of 2.3 procedures. The lowest clearance rates were observed in lower calyx calculi (87.2%) and multiple calyx calculi (83.5%). The overall complication rate was 15.1%, and the most common complication was postoperative fever (9.6%). One patient required blood transfusion, owing to postoperative coagulation disorders induced by urosepsis.Single or staged FURS is a practical treatment option for the renal stones sized 2 to 4 cm with acceptable efficacy and safety. Stone clearance rate of FURS treatment is mainly affected by stone size and location.

Background: This study was performed to determine the association of frailty and comorbidity status with postoperative morbidity and mortality in patients with acute mesenteric ischemia (AMI)., Methods: Patients diagnosed with AMI between April 2006 and September 2019 were enrolled in this study. Frailty was evaluated by sarcopenia which was diagnosed by third lumbar vertebra psoas muscle area (PMA). Comorbidity status was evaluated by the Charlson Comorbidity Index (CCI) score. Univariate and multivariate analyses evaluating the risk factors for postoperative morbidity and mortality were performed., Results: Of the 174 patients, 86 were managed conservatively and 88 underwent surgery. In surgically managed patients, 39.8% developed complications within 30 days of surgery. Ten patients died within 30 days of the operation. In the univariate analyses, white blood cell >10 g/L, low PMA, CCI score ≥2, and bowel resection were associated with postoperative complications. Multivariate analysis revealed that low PMA, CCI score ≥2, and bowel resection were independent predictors of postoperative complications., Conclusions: This study demonstrated that low PMA, CCI score ≥2, and bowel resection were independent risk factors for postoperative complications in patients with AMI. Preoperative assessment of frailty using PMA and the evaluation of comorbidity status using CCI may serve as helpful tools in preoperative risk assessment and should be integrated into scoring systems for surgically treated AMI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To discuss the sensitivity and specificity of the combinations of multiple factors that work on bone infection after artificial joint, and provide evidence-based medical basis for the early diagnosis of infection after artificial joint., Methods: A retrospective review was conducted on 35 patients diagnosed with periprosthetic joint infections (PJI) or aseptic loosening (AL) who both received revision operation from January 2011 to January 2015. Analyzing and comparing their epidemiology indexes and expounded a series of auxiliary examinations corresponding positive diagnosis ratio., Results: Thirty-five patients were divided into two groups. One is called group PJI which includes 16 patients, and the other is called group AL which contains 19 patients. There was no statistical difference between in age (p = 0.536), gender ratio (p = 0.094), and the time of catching infection or getting loose (p = 0.055). Swelling was statistical significant (p = 0.0435 < 0.05). AUC of CRP = 0.947, ESR = 0.893, IL-6 = 0.893, PCT = 0.781, WBC = 0.839, and PMN = 0.755, respectively, CRP has a high diagnostic value to PJI, ESR, IL-6, PCT, WBC, and PMN% possess a moderate diagnostic value. There were 3 cases of PJI whose pathological paraffin section showed infectious inflammatory cells (100%). three PJI patients and one AL patient whose 99mTc-MDP examination presented 100% infection or looseness rate., Conclusion: CRP has a high diagnostic value to PJI. Histopathology HE staining, Gram staining, and 99mTc-MDP provide a highly accurate diagnosis for PJI. Therefore, the results suggest combining the unique clinical symptoms of PJI patients with relevant laboratory indexes, histopathologic characteristics, and imageological examinations that can improve diagnostic sensitivity and specificity of PJI in its early stage.

Purpose: This study aims to explore the relationship between miR-195 and CD40 and its effect on Th17/Treg balance in rats with non-alcoholic fatty liver disease (NAFLD)., Methods: We established rat models of NAFLD and made seven groups, Normal group (without modeling), Model group (model rats), NC group (model rats injected with negative control vector), miR-195 OE group (model rats injected with miR-195 mimic), anti-miR-195 group (model rats injected with miR-195 inhibitor), Si-CD40 group (model rats injected with CD40 silencing vector), and anti-miR-195+Si-CD40 group (model rats injected with miR-195 inhibitor and CD40 silencing vector). Dual-luciferase reporter gene assay verified the targeting relationship between miR-195 and CD40. The mRNA and protein expression levels of miR-195, CD40 as well as Th17/Treg associated cytokines in the liver tissues were detected. The pathological changes of liver tissues were detected, and the liver lesion scoring was carried out. The liver coefficient was calculated. The levels of liver function related indices, and Th17/Treg associated cytokines and inflammatory factors in serum were determined. The proportions of Th17/Treg cells in serum were determined by flow cytometry., Results: Compared with Normal group, miR-195 expression level in liver tissues of rats in other six groups was significantly reduced (all P < 0.05); the serum levels of AST, ALT, GGT, IL-17, TNF-α, IL-23, IL-6, IL-8, TC, TG, HDL, and LDL, and the Th17/Treg ratio, as well as the mRNA and protein expression levels of CD40, RORyt, IL-17, TNF-α, IL-23, and IL-8 in liver tissues were significantly increased (all P < 0.05); while the mRNA and protein expression levels of Foxp3, and IL-10 level were significantly reduced (all P < 0.05). Compared with Model group, the above parameters showed an opposite trend in miR-195 OE group and Si-CD40 group were significantly reduced (all P < 0.05). Moreover, anti-miR-195 group could aggravate the imbalance of Th17/Treg cells in rats with NAFLD and promote inflammatory response. Compared with anti-miR-195 group, the combined treatment in anti-miR-195+Si-CD40 group can partially avoid the imbalance of Th17/Treg cells, and inhibit inflammatory response., Conclusion: Overexpression of miR-195 can reduce the Th17/Treg ratio to maintain Th17/Treg balance by inhibiting CD40 expression in rats with NAFLD., Competing Interests: Declaration of Competing Interest All the authors declared no conflicts of interest concerning this article., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To compare postoperative short-term outcomes and long-term prognosis between perioperative Enhanced Recovery After Surgery (ERAS) and conventional pathways protocols in gastric cancer patients. Methods: This is a single institute retrospective cohort study, all patients were pathologically proved to be gastric adenocarcinoma, underwent standard radical gastrectomy with D2 lymphadenectomy during the period of 2007-2012. Total 2124 cases were eligible to be analysed and divided into ERAS groups and Non-ERAS group according to the different perioperative pathway protocol. Propensity score matching method (in SPSS, 24.0 version, IBM Company) was used to balance the baseline characteristics. Two groups were matched in a 1∶1 ratio. There were 521 cases per group after matched. The short-term clinical outcomes (postoperative complications, length of hospital stay, blood loss, 30-day re-admission rate, etc.) and overall 5-year survival rates were compared between the two groups. Results: The incidence of overall postoperative complications was similar between the two groups (ERAS group=18.4%, non-ERAS group=19.4%, P= 0.69), including anastomotic leakage, abdominal hemorrhage, etc. But the incidence of SSI, atelectasis, and thromboembolic disease in ERAS group was significant lower than that in Non-ERAS group. The number of lymph node harvested, operation time, intraoperative blood loss, postoperative hospital and cost in ERAS group were better than those in non-ERAS group. There were no significant differences in unplanned reoperation (ERAS group = 3.1%, non-ERAS group = 2.1%, P= 0.33), 30 day readmission rate of discharge (ERAS group = 6.1%, non-ERAS group = 5.6%, P= 0.69) and postoperative mortality (ERAS group = 0.4%, non-ERAS group = 0.2%, P= 0.56) between the two groups. The 5-year overall survival rates of non-ERAS group and ERAS group were 66.2% and 72.8% respectively ( P= 0.007). The subgroup analysis found that 5-year OS rates of stage I were 93.4% and 92.7% ( P= 0.73), these of stage Ⅱ and Ⅲ were 82.2% vs 75.2% ( P= 0.007) and 47.6% vs 35.7% ( P= 0.02) in ERAS group and non-ERAS group respectively. Conclusions: Perioperative ERAS pathway management is safe and feasible for patients with gastric cancer, without increasing the incidence of complications and 30-day readmission rate. This protocol can improve the prognosis of patients with gastric cancer.

Background/purpose: Pediculus capitis is the most common human ectoparasite. When it feeds on the blood through the scalp of its host, the anticoagulant in its saliva causes scalp inflammation and itching, and consequent scratching by the host causes further inflammation from bacterial infection. P. capitis infestation is currently a common parasitic dermatosis and a critical public health concern in underdeveloped countries., Methods: Through naked eye inspection of P. capitis on or in the hair from 323 school children in Cambodia., Results: A total of 143 children (44.3%) were found to have P. capitis infestation. Univariate analysis revealed that girls had a significantly higher infection rate than boys. Overall, young aged schoolchildren (10 yrs old ≤) showed significantly higher infection rate than old aged schoolchildren (>10 yrs old). Groups stratified by time revealed that schoolchildren studied at the afternoon classes than morning classes in Tuol Prum Muoy Primary School had a significantly higher risk in acquisition of P. capitis infestation. Multivariate analysis results indicated that relative to the boys, the girls were at a significantly higher risk of contracting P. capitis infection. When stratified by inspection time with the Tuol Prum Muoy Primary School morning classes as the reference, the Tuol Prum Muoy Primary School afternoon classes exhibited a significantly higher risk of P. capitis infection., Conclusion: Primary school children in Cambodia have a high P. capitis infection rate and thus require effective treatment and prevention measures to treat symptoms and lower the infection rate., (Copyright © 2017. Published by Elsevier B.V.)

Glucocorticoid-Induced Osteoporosis (GIOP) is a prevalent clinical complication caused by large dose administration of glucocorticoids, such as Dexamethasone (Dex) and Prednisone. GIOP may lead to fractures and even Osteonecrosis of the Femoral Head (ONFH). It has been reported that glucocorticoids inhibit osteogenesis via the suppression of osteogenic differentiation in Mesenchymal Stem Cells (MSCs), but the precise mechanism underlying this suppression awaits further investigation. Meanwhile, novel and efficacious therapies are recommended to cope with GIOP. In this study, we demonstrated that Dex had the inhibitory effect on Bone Morphogenetic Protein 9 (BMP9)-induced ALP activities and matrix mineralization in Mouse Embryonic Fibroblasts (MEFs). In addition, the study confirmed that Dex decreased the expression of osteogenic markers such as Runx2 and OPN. However, the inhibitory effect of Dex on these osteogenic markers can be reversed when combined with insulin-like growth factor 1 (IGF-1). Regarding the inhibitory mechanism, we found that the level of AKT and p-AKT can be decreased by Dex and that Ly294002, the PI3K inhibitor, can block the reversal effect of IGF-1. Moreover, the knockdown or inhibition of COX-2 produced similar results to those of Ly294002. Our findings indicated that IGF-1 may reverse the osteogenic inhibitory effect of Dex via PI3K/AKT pathway, which may be associated with the up-regulation of COX-2. This study may provide new clinical management strategy for GIOP cases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Due to both the hidden nature and the irreversibility of Alzheimers disease (AD), it has become the killer of the elderly and is thus the focus of much attention in the medical field. Radiologists compare the predicted brain age with the ground truth in order to provide a preliminary analysis of AD, which helps doctors diagnose AD as early in its development as possible. In this paper, a transfer learning-based method of predicting brain age using MR images and dataset of a public brain was proposed. In order to get the best transfer results, we froze different layers and only fine-tuned the remaining layers. We used three planes of brain MR images together to predict age for the first time and experiment results showed that the proposed method performs better than the state-of-the-art method under mean absolute error metric by 0.6 years. In addition, to explore the relationship between brain MR images of different planes and predicted age accuracy, we used three different planes of brain MR images to predict age respectively for the first time and found that sagittal plane MR images outperformed two other planes in age estimation. Finally, our research identified, the effective regions that contribute to brain age estimation for cognitively normal individuals and for AD patients with deep learning. For AD patients, the effective region is mainly concentrated in the frontal lobe of the brain, verifying the relevant medical conclusions about AD.

Nanocarriers with strong tumor cell targeting ability have been expected to overcome limitations of cancer chemotherapy. Herein, cell membrane mimetic micelles were prepared from a random copolymer (PMNCF) containing cell membrane phosphorylcholine zwitterion, cholesterol, and tumor cell targeting folic acid (FA) at the side chain ends. Surface orientation of the FA ligand was optimized during PMNCF micelle preparation by controlling solvent solubility for FA. The out-oriented ligands on the micelles were immobilized by the strongly associated hydration layer around the closely packed phosphorylcholine zwitterions. The doxorubicin (DOX) loaded PMNCF micelles were demonstrated to reduce normal cell toxicity to less than 20%. More significantly, HeLa and MCF-7 tumor cell killing efficacy of the optimized formulation was enhanced to 160% compared with that of free DOX. The excellent performances of the drug loaded PMNCF micelles on both tumor cell killing and normal cell toxicity reducing efficacies reveal great potential for developing advanced drug delivery system.

Objective: This study aims to investigate the effect of different concentrations of docosahexaenoic acid (DHA) on proliferation and apoptosis in HepG2 cell lines, and to research the possible molecular mechanisms., Methods: DHA concentration was 0 g/mL in the negative control group, and 15, 30, 45, 60 and 75 ug/mL, respectively, in the experimental groups. CCK-8 and flow cytometry methods were used to observe the growth inhibition and apoptosis rates of HepG2 cells cultured in vitro , which were treated with different concentrations of DHA. The level of β-catenin and c-myc mRNA and protein were measured by real-time PCR and western blot, respectively., Results: In the concentration range of 0-45 ug/mL, the action time was 24 hours. DHA could inhibit the growth of HepG2 cells, and there were significant differences between the experimental and control groups ( P <0.01). The same was observed in each of the two groups in experimental groups. As drug concentration or action time increased, results revealed no statistical differences. Furthermore, flow cytometric analysis indicated that DHA could promote HepG2 cell apoptosis; and the apoptosis rate was greatly different between the experimental and control groups ( P <0.01). The same was observed in each of the two groups in the experimental groups. Real-time PCR could detect low c-myc expression in HepG2 cells disposed by DHA, and c-myc expression was significantly different between the experimental and control groups ( P <0.01). The same was observed in each of the two groups in the experimental groups. There was no obvious difference in β-catenin expression between the experimental and control groups, and the experimental groups were all identical. Western blot demonstrated that DHA could decrease β-catenin and c-myc protein expression in HepG2 cells., Conclusion: DHA could promote apoptosis and inhibit the proliferation of HepG2 cells. The possible mechanism was related with the down-regulated protein expression of β-catenin and the mRNA expression of c-myc., (© 2019 by the Association of Clinical Scientists, Inc.)

Glioma remains the leading cause of brain tumor-related death worldwide, and radiation is a standard adjuvant therapy with proven efficacy. Salvianolic acid B (SalB), a bioactive compound isolated from Radix Salviae, has been shown to exert anti-cancer effects in many cancer cell lines, including glioma. This study aimed to investigate whether SalB could affect response to radiation in human glioma cells. We found that SalB decreased cell viability of U87 cells in a-dose-dependent manner. A subthreshold dose of SalB at 0.5 μM, which had no effect on cell viability and apoptosis, significantly increased radiation sensitivity of U87 cells in a dose- and time-dependent manner, but had no effect on sensitivity to temozolomide (TMZ). Similar results were also observed in human glioma U373 cells. In addition, SalB aggravated the radiation-induced apoptosis and mitochondrial dysfunction, as measured by mitochondrial Ca 2+ buffering capacity and mitochondrial swelling. SalB treatment markedly promoted mitochondrial fission and differently regulated the expression of fission proteins. Furthermore, downregulation of the fission protein Fis-1 using siRNA was found to partially reversed the SalB-induced effects on cell viability, apoptosis and mitochondrial fission in U87 cells. In conclusion, our results suggest that a subthreshold dose of SalB renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction, and radiotherapy combined with SalB might be a novel treatment for glioma patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the effect of microRNA-210 on the spinal cord injury (SCI) and its underlying mechanism., Materials and Methods: The mouse SCI model was established. Mice were randomly assigned into 4 groups, namely the sham operation group (sham group), surgery group (SCI group), surgery+NC group (SCI+NC group) and surgery+microRNA-210 overexpression group (SCI+microRNA-210 mimics group). The mRNA levels of microRNA-210 and the key genes in the JAK-STAT pathway of the four groups were detected by Real-Time Polymerase Chain Reaction (RT-PCR) at different time points. Protein levels of JAK2 and STAT3 in mice of the four groups were detected by Western blot. To investigate the role of microRNA-210 in SCI recovery, changes in the motor function of mice were detected., Results: Grip strengths of right and left forelimbs in mice from the sham group were temporarily decreased at the early stage after surgery, which were gradually recovered to the preoperative levels on the 3rd postoperative day. However, mice in SCI group were unable to complete the grip strength determination at the early stage after surgery. Mice in SCI group were capable of grasping on the 7th postoperative day. Besides, grip strengths of mice in SCI group were remarkably lower than those of sham group until the end-point (on the 50th day). Furthermore, mRNA levels of microRNA-210 in mice of SCI group were decreased in a time-dependent manner (p<0.05). Higher grip strengths were observed in mice of SCI+microRNA-210 mimics group in comparison with those of SCI group and SCI+NC group (p<0.05). In addition, Western blot showed that protein levels of JAK2 and STAT3 in mice of SCI group were increased in a time-dependent manner (p<0.05). Moreover, protein levels of JAK2, STAT3, and MCP-1 in mice of SCI+NC group were remarkably higher than those in the sham group and SCI+microRNA-210 mimics group (p<0.05)., Conclusions: MicroRNA-210 is down-regulated in SCI mice. Grip strengths of SCI mice can be recovered after microRNA-210 overexpression via inhibiting inflammatory response by the JAK-STAT pathway.