Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.

Background and aims: A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC. Methods: The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy. Results: In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, p<0.001 and z=16.17, p<0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, p<0.001 and z=49.17, p<0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line. Conclusion: Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Effect of robot-assisted gait training on motor dysfunction in Parkinson's patients:A systematic review and meta-analysis.

BACKGROUND: Robot-assisted gait training (RAGT) has been reported to treat motor dysfunction in patients with Parkinson's disease (PD) in the last few years. However, the benefits of RAGT for treating motor dysfunction in PD are still unclear. OBJECTIVES: To investigate the efficacy of RAGT for motor dysfunction in PD patients. METHODS: We searched PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, Chinese Biomedical Literature Database (CBM), and Chinese VIP Database for randomized controlled trials investigating RAGT to improve motor dysfunction in PD from the databases' inception dates until September 1, 2022. The following outcome indexes were employed to evaluate motor dysfunction: the Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), 10-Meter Walk Test gait speed (10-MWT), gait speed, stride length, cadence Unified Parkinson Disease Rating Scale Part III (UPDRS III), 6-Minute Walk Test (6MWT), and the Timed Up and Go test (TUG). The meta-analysis was performed using the proper randomeffect model or fixed-effect model to evaluate the difference in efficacy between the RAGT and the control groups. The Cochrane Risk of Bias Tool was used for the included studies and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to interpret the certainty of the results. RESULTS: The results consisted of 17 studies comprising a total of 670 participants. Six hundred and seven PD patients with motor dysfunction were included: 335 in the RAGT group and 335 in the control group. This meta-analysis results established that when compared with the control group, robot-assisted gait training improved the BBS results of PD patients (MD: 2.80, 95%CI: 2.11-3.49, P< 0.00001), ABC score (MD: 7.30, 95%CI: 5.08-9.52, P< 0.00001), 10-MWT (MD: 0.06, 95%CI: 0.03-0.10, P= 0.0009), gait speed (MD: 3.67, 95%CI: 2.58-4.76, P< 0.00001), stride length (MD: 5.53, 95%CI: 3.64-7.42, P< 0.00001), cadence (MD: 4.52, 95%CI: 0.94-8.10, P= 0.01), UPDRS III (MD: -2.16, 95%CI: -2.48--1.83, P< 0.00001), 6MWT (MD: 13.87, 95%CI: 11.92-15.82, P< 0.00001). However, RAGT did not significantly improve the TUG test result of patients with PD (MD =-0.56, 95% CI: -1.12-0.00, P= 0.05). No safety concerns or adverse reactions among robot-assisted gait training patients were observed. CONCLUSION: Even though RAGT can improve balance function, walking function, and gait performance and has demonstrated positive results in several studies, there is currently insufficient compelling evidence to suggest that it can improve all aspects of lower motor function.

Quenching thirst with poison? Paradoxical effect of anticancer drugs.

Anticancer drugs have been developed with expectations to provide long-term or at least short-term survival benefits for patients with cancer. Unfortunately, drug therapy tends to provoke malignant biological and clinical behaviours of cancer cells relating not only to the evolution of resistance to specific drugs but also to the enhancement of their proliferation and metastasis abilities. Thus, drug therapy is suspected to impair long-term survival in treated patients under certain circumstances. The paradoxical therapeutic effects could be described as 'quenching thirst with poison', where temporary relief is sought regardless of the consequences. Understanding the underlying mechanisms by which tumours react on drug-induced stress to maintain viability is crucial to develop rational targeting approaches which may optimize survival in patients with cancer. In this review, we describe the paradoxical adverse effects of anticancer drugs, in particular how cancer cells complete resistance evolution, enhance proliferation, escape from immune surveillance and metastasize efficiently when encountered with drug therapy. We also describe an integrative therapeutic framework that may diminish such paradoxical effects, consisting of four main strategies: (1) targeting endogenous stress response pathways, (2) targeting new identities of cancer cells, (3) adaptive therapy- exploiting subclonal competition of cancer cells, and (4) targeting tumour microenvironment.

Notopterol Inhibits the NF-κB Pathway and Activates the PI3K/Akt/Nrf2 Pathway in Periodontal Tissue.

Notopterol, an active component isolated from the traditional Chinese medicine Notopterygium incisum Ting ex H.T. Chang, exerts anti-inflammatory activity in rheumatoid arthritis. However, its roles in suppression of inflammatory insults and halting progression of tissue destruction in periodontitis remain elusive. In this study, we reveal that notopterol can inhibit osteoclastogenesis, thereby limiting alveolar bone loss in vivo. In vitro results demonstrated that notopterol administration inhibited synthesis of inflammatory mediators such as IL-1ß, IL-32, and IL-8 in LPS-stimulated human gingival fibroblasts. Mechanistically, notopterol inhibits activation of the NF-κB signaling pathway, which is considered a prototypical proinflammatory signaling pathway. RNA sequencing data revealed that notopterol activates the PI3K/protein kinase B (Akt)/NF-E2-related factor 2 (Nrf2) signaling pathway in LPS-stimulated human gingival fibroblasts, a phenomenon validated via Western blot assay. Additionally, notopterol treatment suppressed reactive oxygen species levels by upregulating the expression of antioxidant genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), catalase (CAT), and glutathione reductase (GSR), indicating that notopterol confers protection against oxidative stress. Notably, inhibition of Akt activity by the potent inhibitor, MK-2206, partially attenuated both anti-inflammatory and antioxidant effects of notopterol. Collectively, these results raise the possibility that notopterol relieves periodontal inflammation by suppressing and activating the NF-κB and PI3K/AKT/Nrf2 signaling pathways in periodontal tissue, respectively, suggesting its potential as an efficacious treatment therapy for periodontitis.

From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

Prediction of biogas production in anaerobic digestion of a full-scale wastewater treatment plant using ensembled machine learning models.

Anaerobic digestion (AD) of sludge is a key approach to recover useful bioenergy from wastewater treatment and its stable operation is important to a wastewater treatment plant (WWTP). Because of various biochemical processes that are not fully understood, AD operation can be affected by many parameters and thus modeling AD processes becomes a useful tool for monitoring and controlling their operation. In this case study, a robust AD model for predicting biogas production was developed using ensembled machine learning (ML) model based on the data from a full-scale WWTP. Eight ML models were examined for predicting biogas production and three of them were selected as metamodels to create a voting model. This voting model had a coefficient of determination (R2 ) at 0.778 and a root mean square error (RMSE) of 0.306, outperformed individual ML models. The Shapley additive explanation (SHAP) analysis revealed that returning activated sludge and temperature of wastewater influent were important features, although they affected biogas production in different ways. The results of this study have demonstrated the feasibility of using ML models for predicting biogas production in the absence of high-quality data input and improving model prediction through assembling a voting model. PRACTITIONER POINTS: Machine learning is applied to model biogas production from anaerobic digesters at a full-scale wastewater treatment plant. A voting model is created from selected individual models and exhibits better performance of predication. In the absence of high quality data, indirect features are identified to be important to predicting biogas production.

A miniature longitudinal-bending hybrid linear ultrasonic motor inspired by the planar hinged five bar mechanism.

Inspired by the double crank planar hinged five bar mechanism, a longitudinal-bending hybrid linear ultrasonic motor with compact miniature is proposed and tested. In order to realize miniaturization, it adopts a bonded-type structure. Four lead zirconate titanate (PZT) piezoelectric ceramics are distributed equally into two groups and bonded to the two ends of the metal frame, and then, two voltages with a phase difference of 90° are applied to each of the two groups of PZT ceramics. Subsequently, the first-order longitudinal vibration and second-order bending vibration generated by the motor combine with each other at the tip of the driving foot to form an elliptical motion trajectory. According to the theoretical kinematic analysis of the free beam, the initial structural dimensions of the motor were designed. Then, the initial dimensions of the motor were optimized, and the zero-order optimization algorithm was used to achieve the purpose of longitudinal and bending resonance of the motor, and finally, the optimal dimensions of the motor were obtained. A prototype of the designed motor was made, followed by experimental tests on the performance of the prototype, including mechanical output. The maximum motor speed without load at 69.4 kHz is 134.57 mm s-1. Under 200 Vpp voltage and 6 N preload, the output thrust of the motor is about 0.4 N at the maximum. The actual mass of the motor is about 1.6 g; therefore, the thrust-to-weight ratio was calculated as 25.

A Bilayer Membrane Doped with Struvite Nanowires for Guided Bone Regeneration.

Guided bone regeneration (GBR) therapy demonstrates a prominent curative effect on the management of craniomaxillofacial (CMF) bone defects. In this study, a GBR membrane consisting of a microporous layer and a struvite-nanowire-doped fibrous layer is constructed via non-solvent induced phase separation, followed by an electrospinning procedure to treat critical-sized calvarial defects. The microporous layer shows selective permeability for excluding the rapid-growing non-osteogenic tissues and potential wound stabilization. The nanowire-like struvite is synthesized as the deliverable therapeutic agent within the fibrous layer to facilitate bone regeneration. Such a membrane displays a well-developed heterogeneous architecture, satisfactory mechanical performance, and long-lasting characteristics. The in vitro biological evaluation reveals that apart from being a strong barrier, the bilayer struvite-laden membrane can actively promote cellular adhesion, proliferation, and osteogenic differentiation. Consequently, the multifunctional struvite-doped membranes are applied to treat 5 mm-sized bilateral calvarial defects in rats, resulting in overall improved healing outcomes compared with the untreated or the struvite-free membrane-treated group, which is characterized by enhanced osteogenesis and significantly increased new bone formation. The encouraging preclinical results reveal the great potential of the bilayer struvite-doped membrane as a clinical GBR device for augmenting large-area CMF bone reconstruction.

Characterization of volatile organic compounds in Polygonum multiflorum and two of its processed products based on multivariate statistical analysis for processing technology monitoring.

Herein we describe a comprehensive analysis of the volatile organic compounds (VOCs) of raw Polygonum multiflorum Thunb. (PM) and two of its processed products, as well as an effective and simple method based on volatile markers to determine to which extent the PM had been processed. Sixty-five VOCs were identified by headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), along with headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Principal component analysis (PCA) of the HS-SPME-GC-MS spectra and fingerprint analysis of the HS-GC-IMS spectra allowed the identification of raw PM from its processed products based the VOCs identified. Furthermore, the content and distribution of VOCs in the samples were easily analyzed visually based on clustering-kernel density estimation (Cluster-KDE). Finally, exploratory factor analysis (EFA) allowed the screening of significant markers to identify the processing method and consequently distinguish the three studied groups of PM.

Granular cell tumor of the appendix: a case report and literature review.

A granular cell tumor (GCT) is an unusual benign soft tissue tumor that can occur at any age and in any part of the body. GCTs are mostly found in the skin and subcutaneous tissues, bronchi, esophagus, breast tissue, and tongue. A GCT originating in the digestive tract, particularly in the appendix, is relatively rare and usually diagnosed as an incidental finding. We herein describe the first case of abdominal distension and occasional pain secondary to a GCT of the appendix in our hospital. The findings from this case suggest that a GCT of the appendix is a rare entity for which surgical resection is an efficient therapy.

Mendelian Randomization Rules Out Causation Between Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease.

Background: Inflammatory bowel disease (IBD) and non-alcoholic fatty liver disease (NAFLD) usually co-exist clinically. However, whether such association is causal is still unknown. Methods: Genetic variants were extracted as instrumental variables from the largest genome-wide association study (GWAS) of IBD, Crohn's disease (CD) and ulcerative colitis (UC) with 25,042 cases and 34,915 controls (GWAS p-value < 5 × 10-8). Information of genetic variants in NAFLD was extracted from a GWAS with 1,483 cases and 17,781controls. Also, liver fat content (LFC) was included as the outcome. Then, a bi-direction Mendelian randomization (MR) was carried out to appraise the causal relationship between NAFLD on IBD. Besides, a multivariable MR (MVMR) design was carried to adjust for body mass index (BMI) and type 2 diabetes (T2D) as well. Results: Generally, IBD might not affect the risk of NAFLD (OR = 0.994 [0.970, 1.019]), together with its subtypes including UC and CD. However, genetically-elevated risk of IBD might cause liver fat accumulation (beta = 0.019, p-value = 0.016) while turning insignificant at Bonferroni correction. Besides, no causal effect of NAFLD on IBD was observed (OR = 0.968 [0.928, 1.009]), together with UC and CD. Also, genetically-elevated LFC could not impact IBD, UC and CD either. The MR CAUSE analysis supported these null associations and MVMR analysis also supported such null associations even after adjusting for BMI and T2D. Conclusion: This MR study ruled out the causal relationship between IBD and NAFLD, suggesting therapeutics targeting NAFLD might not work for IBD and vice versa.

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+ T cells in mice.

Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.

Efficacy and Safety of Lenalidomide Monotherapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma: Systematic Review and Meta-Analysis.

INTRODUCTION: Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes. RESULTS: We included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months. CONCLUSION: This study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.

Disseminated Coinfection by Mycobacterium fortuitum and Talaromyces marneffei in a Non-HIV Case.

BACKGROUND: Mycobacterium fortuitum is a rapidly growing non-tuberculous mycobacterium (NTM) with weak pathogenicity. Here, we present a rare case of disseminated M. fortuitum and Talaromyces marneffei coinfection in a human immunodeficiency virus (HIV) negative patient. CASE PRESENTATION: A 28-year-old female was admitted to our hospital due to 2 months of swelling of lymph nodes on the right side of her cervix, accompanied by repeated low fever for more than 1 month. Biopsy of the right cervical lymph node and endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) both suggested granulomatous inflammation. The bacterial culture and mycobacteria examination of the lesion as well as HIV antibody test were all negative. Disseminated T. marneffei infection was diagnosed by the quantitative polymerase chain reaction (qPCR) results from the blood showing 1798 copies/ul. In the meantime, treatment with amphotericin B combined with cefoxitin was administered for suspected NTM infection. However, the once-dropped fever recurred and the lymph nodes continued to swell. Metagenomics next-generation sequencing (mNGS) detection of the lymph nodes indicated M. fortuitum. After combination treatment with amphotericin B, voriconazole, linazolamide, and imipenem, the patient's body temperature returned to normal, the lymph node swelling was gradually reduced, and the lung lesion was absorbed. CONCLUSION: We report the first case of an HIV-negative patient diagnosed with disseminated M. fortuitum and T. marneffei coinfection with nonspecific clinical manifestation, in order to heighten awareness of these infections.

MiR-520b inhibits proliferation, migration and invasion in gallbladder carcinoma by targeting RAB22A.

INTRODUCTION: Previous studies have reported that miR-520b exhibited inhibitory effects on various human tumors, whereas the effects of miR-520b on gallbladder carcinoma (GBC) have remained unclear. To investigate the effects of miR-520b on GBC progression and reveal the underlying mechanisms, this study was performed. MATERIAL AND METHODS: MiR-520b and RAB22A mRNA levels were analyzed by quantitative real-time PCR (qPCR). RAB22A protein level was analyzed via Western blot and immunohistochemical (IHC) analysis. The proliferation, colony formation ability, migration and invasion of NOZ cells were measured via MTT, colony formation, wound healing and transwell invasion assay respectively. RESULTS: MiR-520b expression level was lower in human GBC tissues than that in neighboring normal tissues. MiR-520b mimic repressed NOZ cell proliferation, colony formation ability, migration and invasion, whereas miR-520b inhibitor exhibited opposite effects. Dual luciferase reporter assay confirmed that miR-520b could bind to the 3'-untranslated regions of RAB22A mRNA. Moreover, RAB22A overexpression significantly abolished the anti-tumor effects of miR-520b in a NOZ cell model. Western blot, qPCR and IHC analysis proved that human GBC tissues showed a higher RAB22A expression level than neighboring normal tissues. Additionally, there was a negative association between miR-520b and RAB22A expression. CONCLUSIONS: MiR-520b had suppressive effects on GBC via targeting RAB22A in vitro.

The effect of platelet-rich plasma on the fusion rate and clinical outcome of spinal fusion surgery: A systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is widely used in many orthopedic surgeries and spinal disease treatments; however, the effect of PRP on spinal fusion remains controversial. QUESTIONS/PURPOSES: To assess the fusion rate and clinical results of PRP compared with non-PRP administration in the treatment of spinal fusion with regard to decreasing pain and improving healing and function. PATIENTS AND METHODS: Studies comparing PRP to non-PRP treatment with respect to the fusion rate and clinical outcome in patients who underwent spinal fusion surgery were included. RESULT: Three randomized controlled trials (RCTs) and 7 prospective cohort studies were identified. The spinal fusion rate was not significantly different between the groups in all RCTs or cohort studies at the final follow-up. In comparison, PRP significantly reduced pain after surgery as evaluated in the RCT analysis and the complication rate did not differ significantly between the two groups. CONCLUSION: According to the available studies, PRP does not contribute to the union rate, relieve pain or increase the complication rate in spinal fusion surgery. As clinical heterogeneity exists in these studies, further large, well-designed RCTs that focus on the standard assessment of PRP are needed.

Hepatic epithelioid hemangioendothelioma: Update on diagnosis and therapy.

With an estimated incidence of only 1-2 cases in every 1 million people, hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types: solitary, multiple, and diffuse. Both the etiology and characteristic clinical manifestations of HEHE are unclear. However, HEHE has a characteristic appearance on imaging including ultrasound, magnetic resonance imaging, and positron emission tomography/computerized tomography. Still, its diagnosis depends mainly on pathological findings, with immunohistochemical detection of endothelial markers cluster of differentiation 31 (CD31), CD34, CD10, vimentin, and factor VIII antigen as the basis of diagnosis. Hepatectomy and/or liver transplantation are the first choice for treatment, but various chemotherapeutic drugs are reportedly effective, providing a promising treatment option. In this review, we summarize the literature related to the diagnosis and treatment of HEHE, which provides future perspectives for the clinical management of HEHE.

Fast-growing epithelioid hemangioendothelioma of the liver: A case report.

RATIONALE: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS: A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS: HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS: The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES: She remained disease-free throughout a year follow-up period. CONCLUSION: HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.