IL-22, a vital cytokine in autoimmune diseases.

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

Association between the Systemic Immune-Inflammation Index and Thyroid Function in U.S. Adults.

Background: The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results: Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (ß = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (ß = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (ß = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion: Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis.

BACKGROUND/AIMS: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. METHODS: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. RESULTS: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). CONCLUSION: IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Development and validation of a diabetic retinopathy risk prediction model for middle-aged patients with type 2 diabetes mellitus.

Objectives: The study aims to establish a predictive nomogram of diabetic retinopathy(DR) for the middle-aged population with type 2 diabetes mellitus (T2DM). Methods: This retrospective study screened 931 patients with T2DM between 30 and 59 years of age from the 2011-2018 National Health and Nutrition Examination Survey database. The development group comprised 704 participants from the 2011-2016 survey, and the validation group included 227 participants from the 2017-2018 survey. The least absolute shrinkage and selection operator regression model was used to determine the best predictive variables. The logistic regression analysis built three models: the full model, the multiple fractional polynomial (MFP) model, and the stepwise (stepAIC) selected model. Then we decided optimal model based on the receiver operating characteristic curve (ROC). ROC, calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were used to validate and assess the model. An online dynamic nomogram prediction tool was also constructed. Results: The MFP model was selected to be the final model, including gender, the use of insulin, duration of diabetes, urinary albumin-to-creatinine ratio, and serum phosphorus. The AUC was 0.709 in the development set and 0.704 in the validation set. According to the ROC, calibration curves, and Hosmer-Lemeshow test, the nomogram demonstrated good coherence. The nomogram was clinically helpful, according to DCA. Conclusion: This study established and validated a predictive model for DR in the mid-life T2DM population, which can assist clinicians quickly determining who is prone to develop DR.

Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways.

Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-ß) is well known for its anti-proliferative efficacy in diverse cancers. IFN-ß also displayed potent antitumor effects in malignant glioma. IFN-ß affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-ß on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-ß between human GSCs and normal NSCs. We found that IFN-ß preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-ß treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-ß stimulation. We also found that continuous IFN-ß stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-ß treatment. These results may contribute to improve the applications of IFN-ß in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

Genome-based taxonomy of genera Halomicrobium and Halosiccatus, and description of Halomicrobium salinisoli sp. nov.

The genera Halosiccatus and Halomicrobium are the most closely related genera within the family Haloarculaceae (class Halobacteria). All species of these two genera are closely related to each other in phylogenetic analyses based on their 16S rRNA gene sequences, and also using the sequences of four housekeeping genes. The genus Halosiccatus was proposed based on inferred phylogeny using only one of the three distinct 16S rRNA genes detected in strain DC8T, while Halomicrobium zhouii, one of three species of Halomicrobium, was omitted from the reference species used in these analyses. The related 16S rRNA gene sequence similarities of type strains of Halomicrobium katesii and Halomicrobium mukohataei were as high as 99.5%-99.7%, much higher than the threshold values proposed as species boundaries. These issues could have resulted in taxonomic inaccuracies in the genera Halosiccatus and Halomicrobium, and a thorough study was undertaken to clarify the status of all species in both genera. Based on phylogenetic and phylogenomic analyses, the current four species of the two genera form a single clade with high bootstrap confidence, indicating that the genus Halosiccatus should be merged with Halomicrobium. Halomicrobium katesii Kharroub et al. 2008 is proposed as a later heterotypic synonym of Halomicrobium mukohataei (Ihara et al. 1997) Oren et al. 2002. An additional species is also described (strains LT50T and TH30), and was isolated from different Gobi saline soil samples of Tarim Basin, Xinjiang, China. Phenotypic, chemotaxonomic, genomic and phylogenetic properties indicated that strains LT50T (=CGMCC 1.15187T = JCM 30837T) and TH30 (=CGMCC 1.15189 = JCM 30839) represent a novel species of the genus Halomicrobium, for which the name Halomicrobium salinisoli sp. nov. is proposed.

Halobaculum rubrum sp. nov., an extremely halophilic archaeon isolated from a salt lake.

A halophilic archaeal strain, designated C46T, was isolated from an inland salt lake in Qinghai Province, PR China. Results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain C46T belongs to the genus Halobaculum, and the closest phylogenetic relative is Halobaculum gomorrense DSM 9297T with 97.7 % similarity. Despite this, strain C46T was more related to Halobaculum saliterrae WSA2T than other members of the genus Halobaculum based on genome comparison and analysis, and the average nucleotide identity, in silico DNA-DNA hybridization, amino acid identity and percentage of conserved protein values between the two strains were 89.1, 53.3, 89.2 and 75.6 %, respectively, which are lower than the cutoff values proposed for species delimitation. The physiological, biochemical, genetic and genomic characteristics of strain C46T were different from those of its closest phylogenetic neighbours, which indicated that this strain represents a novel species of the genus Halobaculum, for which the name Halobaculum rubrum sp. nov. is proposed. The type strain is C46T (=CGMCC 1.13737T=JCM 32959T).

[Ecological network construction and optimization in Foshan City, China]. / 佛山市生态网络构建及优化.

Under the background of rapid urbanization, the problem of fragmented habitat patches in economically developed areas is particularly prominent, where biodiversity is seriously threa-tened. Therefore, the construction of ecological network is an important measure to connect habitat patches and protect biological habitats. We extracted ecological source areas of Foshan City by using the connectivity index and morphological spatial pattern analysis (MSPA). Potential ecological corridors were identified based on InVEST model and minimal cumulative resistance (MCR). Combining the radiation channels extracted from hydrological analysis to build an ecological network in Foshan City. The ecological network was optimized by adding ecological source areas, stepping stones, and identifying fracture points. Finally, the network before and after optimization was evalua-ted from the aspects of both structure and function based on network analysis method and circuit theory. The results showed that ecological network in Foshan City was composed of 10 ecological source areas, 8 important corridors, 37 general corridors, and 11 radiation channels. After optimization, 7 new ecological source areas, 17 planning corridors, 13 stepping stones, and 80 fracture points were added. After optimization, the ecological network closure, the line rate index and the connection degree index were 0.59, 1.94, and 0.73, respectively. The maximum current density increased from 1.39 to 9.66 after optimization, indicating that the optimized ecological network structure was more perfect and highly connective.

KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer.

Kinesin family member 18A (KIF18A) is significantly overexpressed and is related to the poor prognosis of human cancers. However, the function of KIF18A in esophageal cancer (EC) is still unclear. Human EC cell lines were used in this study. KIF18A expression in human tissues was assessed using Gene Expression Profiling Interactive Analysis 2.0 (GEPIA2). The expressions of KIF18A or IGF2BP3 in EC cells were detected using qRT-PCR or WB. Cells were transfected using si-KIF18A, si-IGF2BP3, and plasmid IGF2BP3. The abilities of proliferation, migration, and invasion were detected by EdU, wound-healing, and transwell assay. The interaction between KIF18A and IGF2BP3 was predicted by starBase v3.0 and studied by RIP and RNA stability assay. Colony formation assay was used to reflect the changes of radiosensitivity in EC cells. KIF18A was upregulated in EC, and KIF18A knockdown inhibited EC cell proliferation, migration, invasion, and radioresistance. The prediction in starBase and RIP assay results showed that KIF18A mRNA could bind to IGF2BP3 protein in EC cells. RNA stability assay was performed to confirm that IGF2BP3 affects mRNA stability of KIF18A. Further studies also showed that IGF2BP3 could positively regulate KIF18A on proliferation, migration, invasion, and radioresistance. Our findings first revealed an oncogenic effect of KIF18A in human EC progression. KIF18A expression was associated with radioresistance of EC cells. The binding relationship between KIF18A and IGF2BP3 might influence the mRNA stability of KIF18A in EC cell lines.

Pregnancy outcomes of infertile women with ultrasound-diagnosed adenomyosis for in vitro fertilization and frozen-thawed embryo transfer.

OBJECTIVE: This study aimed to investigate the effect of ultrasound-diagnosed adenomyosis on assisted pregnancy outcomes, i.e., in vitro fertilization-embryo transfer (IVF-ET). METHODS: This was a retrospective cohort study of 18,568 women who had received their first frozen-thawed ET cycle in Center of Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi and the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital from January 2014 to May 2019. A total of 5,087 patients met the inclusion and exclusion criteria, and they were divided into two groups: adenomyosis with tubal factor infertility (study group, n = 193) and only tubal factor infertility (control group, n = 4894). After a 1:1 propensity score match (caliper value = 0.005), 360 cases were matched in the end. RESULT: There was no statistical difference in the embryo implantation rate, clinical pregnancy rate, or multiple pregnancy rate between the two groups (28.4% vs. 31.7%, 42.2% vs. 42.8%, and 11.7% vs. 12.8%, respectively; P > 0.05). However, the early miscarriage rate in the adenomyosis group was significantly higher than that in the control group (13.3% vs. 5.6%, respectively; P = 0.012). The live birth rate was 22.8% in the women with adenomyosis and was observed to be significantly lower than 33.3% in the control group (P = 0.026). The patients with adenomyosis had a higher incidence of pregnancy complications than those without (4.4% vs. 0.6%, respectively; P = 0.018), but the neonatal birth weight was not related to adenomyosis. CONCLUSION: Women with adenomyosis should be treated as being at high risk of early miscarriage. However, maternal adenomyosis has no effect on the birth weight of the newborn.

A 10-Year Prevalence Survey and Clinical Features Analysis of Pressure Injury in a Tertiary Hospital in China, 2009-2018.

OBJECTIVE: To describe the 10-year prevalence of pressure injury (PI) in a tertiary hospital in China and determine the clinical characteristics of inpatients with PI. METHODS: The authors performed a retrospective analysis of PI cases extracted from the electronic health record of a tertiary hospital. The trend of PI prevalence over 10 years was described by estimating the average percent change (EAPC). Comorbidities were described with the Charlson Comorbidity Index (CCI). The clinical characteristics of PI were described using the number of cases and composition ratio. RESULTS: The overall prevalence of PI was 0.59% (5,838/986,404). From 2009 to 2018, the rate increased from 0.19% to 1.00% (EAPC = 22.46%). When stage I PIs were excluded, the prevalence of PI ranged from 0.15% to 0.79% (EAPC = 21.90%). The prevalence of hospital-acquired PI was 0.13%. Prevalence increased with age (Ptrend < .001) and was significantly higher in men than women (P < .001). Patients with PI were more widely distributed in the ICU (20.58%), vasculocardiology department (11.73%), gastroenterology department (10.18%), and OR (8.29%). Of patients with PI, 71.3% had a CCI score 4 or higher. CONCLUSIONS: The PI prevalence in the study facility increased rapidly over the study period. Pressure injuries among patients in the gastroenterology department and in the community deserve more attention. The CCI may be a good indicator for PI risk assessment.

Enhanced ionic conductivity and lithium dendrite suppression of polymer solid electrolytes by alumina nanorods and interfacial graphite modification.

Poor room-temperature ionic conductivity and lithium dendrite formation are the main issues of solid electrolytes. In this work, rod-shaped alumina incorporation and graphite coating were simultaneously applied to poly (propylene carbonate) (PPC)-based polymer solid electrolytes (Wang et al., 2018). The obtained alumina modified solid electrolyte membrane (Al-SE) achieves a high ionic conductivity of 3.48 × 10-4 S/cm at room temperature with a wide electrochemical window of 4.6 V. The assembled NCM622/Al-SE/Li solid-state battery exhibits initial discharge capacities of 198.2 mAh/g and 177.5 mAh/g at the current density of 0.1 C and 0.5 C, with the remaining capacities of 165.8 mAh/g and 161.3 mAh/g after 100 cycles respectively. The rod-shaped structure of Al2O3 provides fast transport channels for lithium ions and its Lewis acidity promotes the dissociation of lithium salts and release of free lithium ions. The lithiophilic Al2O3 and Graphite form intimate contact with metallic Li and create fast Li+ conductive layers of Li-Al-O layer and LiC6 layer, thus facilitating the uniform deposition of Li and inhibiting Li dendrite formation during long-term cycling. This kind of composite Al-SE is expected to provide a promising alternative for practical application in solid electrolytes.

Preventing Candida albicans from subverting host plasminogen for invasive infection treatment.

Candida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans disseminates into the bloodstream and causes life-threatening systemic infections in immunocompromised patients remains unclear. Plasminogen system activation can degrade a variety of structural proteins in vivo and is involved in several homeostatic processes. Here, for the first time, we characterized that C. albicans could capture and "subvert" host plasminogen to invade host epithelial cell surface barriers through cell-wall localized Eno1 protein. We found that the "subverted" plasminogen system plays an important role in development of invasive infection caused by C. albicans in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting C. albicans Eno1, with high affinity to the 254FYKDGKYDL262 motif in α-helices 6, ß-sheet 6 (H6S6) loop and direct blocking activity for C. albicans capture host plasminogen. mAb 12D9 could prevent C. albicans from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept in vivo studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by Candida spp. In summary, our study provides the evidence of C. albicans invading host by "subverting" plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections.

Femtosecond laser programmed artificial musculoskeletal systems.

Natural musculoskeletal systems have been widely recognized as an advanced robotic model for designing robust yet flexible microbots. However, the development of artificial musculoskeletal systems at micro-nanoscale currently remains a big challenge, since it requires precise assembly of two or more materials of distinct properties into complex 3D micro/nanostructures. In this study, we report femtosecond laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive protein (bovine serum albumin, BSA) as the smart muscle. To realize the programmable integration of the two materials into a 3D configuration, a successive on-chip two-photon polymerization (TPP) strategy that enables structuring two photosensitive materials sequentially within a predesigned configuration was proposed. As a proof-of-concept, we demonstrate a pH-responsive spider microbot and a 3D smart micro-gripper that enables controllable grabbing and releasing. Our strategy provides a universal protocol for directly printing 3D microbots composed of multiple materials.

Dectin-1 Facilitates IL-18 Production for the Generation of Protective Antibodies Against Candida albicans.

Invasive candidiasis (IC) is one of the leading causes of death among immunocompromised patients. Because of limited effective therapy treatment options, prevention of IC through vaccine is an appealing strategy. However, how to induce the generation of direct candidacidal antibodies in host remains unclear. Gpi7 mutant C. albicans is an avirulent strain that exposes cell wall ß-(1,3)-glucans. Here, we found that vaccination with the gpi7 mutant strain could protect mice against invasive candidiasis caused by C. albicans and non-albicans Candida spp. The protective effects induced by gpi7 mutant relied on long-lived plasma cells (LLPCs) secreting protective antibodies against C. albicans. Clinically, we verified a similar profile of IgG antibodies in the serum samples from patients recovering from IC to those from gpi7 mutant-vaccinated mice. Mechanistically, we found cell wall ß-(1,3)-glucan of gpi7 mutant facilitated Dectin-1 receptor dependent nuclear translocation of non-canonical NF-κB subunit RelB in macrophages and subsequent IL-18 secretion, which primed protective antibodies generation in vivo. Together, our study demonstrate that Dectin-1 engagement could trigger RelB activation to prime IL-18 expression and established a new paradigm for consideration of the link between Dectin-1 mediated innate immune response and adaptive humoral immunity, suggesting a previously unknown active vaccination strategy against Candida spp. infection.

Laser Fabrication of Bioinspired Graphene Surfaces With Superwettability.

The past decades have seen growing research interest in developing efficient fabrication techniques for preparing bioinspired graphene surfaces with superwettability. Among the various fabrication methods, laser fabrication stands out as a prominent one to achieve this end and has demonstrated unique merits in the development of graphene surfaces with superwettability. In this paper, we reviewed the recent advances in this field. The unique advantages of laser fabricated graphene surfaces have been summarized. Typical graphene surfaces with superwettability achieved by laser fabrication, including superhydrophobic graphene surfaces, oil/ water separation, fog collection, antibacterial surfaces, surface enhanced Raman scattering (SERS), and desalination, have been introduced. In addition, current challenges and future perspectives in this field have been discussed. With the rapid progress of novel laser physical/ chemical fabrication schemes, graphene surfaces with superwettability prepared by laser fabrication may undergo sustained development and thus contribute greatly to the scientific research and our daily life.

A novel all-fiber-based LiFePO4/Li4Ti5O12 battery with self-standing nanofiber membrane electrodes.

Electrodes with high conductivity and flexibility are crucial to the development of flexible lithium-ion batteries. In this study, three-dimensional (3D) LiFePO4 and Li4Ti5O12 fiber membrane materials were prepared through electrospinning and directly used as self-standing electrodes for lithium-ion batteries. The structure and morphology of the fibers, and the electrochemical performance of the electrodes and the full battery were characterized. The results show that the LiFePO4 and Li4Ti5O12 fiber membrane electrodes exhibit good rate and cycle performance. In particular, the all-fiber-based gel-state battery composed of LiFePO4 and Li4Ti5O12 fiber membrane electrodes can be charged/discharged for 800 cycles at 1C with a retention capacity of more than 100 mAh·g-1 and a coulombic efficiency close to 100%. The good electrochemical performance is attributed to the high electronic and ionic conductivity provided by the 3D network structure of the self-standing electrodes. This design and preparation method for all-fiber-based lithium-ion batteries provides a novel strategy for the development of high-performance flexible batteries.

Questioning the staging of tumor deposits of colorectal cancer in the eighth edition of the TNM classification: validation by prognosis.

Tumor deposits (TD) of colorectal cancer (CRC) in the 8th edition of TNM classification (TNM 8th) were staged as N1c, but the number of TDs was ignored. The aim of this study was to analyze the association of TD with CRC and verify the rationale for TD staging in the TNM 8th. A total of 517 patients with CRC, surgically treated from Aug. 2013 to Dec. 2017, were retrospectively reviewed. Univariate and multivariate analyses were used to observe the correlations between clinicopathologic features and TD. The reasonability of TD staging in TNM 8th was validated by prognostic analysis. The occurrence of TD in CRC was 11.2% (154/1375). Multivariate analysis indicated that T stage (P<0.001, OR = 2.026 and 5.380, 95% CI: 0.917-4.474 and 2.229-12.981 for T3 and T4 respectively) and TNM stage (P<0.001, OR = 9.051 and 16.305, 95% CI: 2.055-39.857 and 3.780-70.323 for TNM II and TNM III respectively) were independent risk factors for TD status. Only degree of differentiation (P = 0.020, OR = 0.197, 95% CI: 0.050-0.774 for poorly differentiated) was an independent risk factor for number of TDs. Survival analysis showed that patients with TD exhibited a significantly worse prognosis compared to patients without TD (P<0.001), and a significant prognostic difference was found among groups TD = 1, TD = 2/3 and TD≥4 (all P<0.05). Patients in T3-4aN1a/1b had a worse prognosis than patients in T3-4aN1c did, although both groups were classified as TNM IIIB (P = 0.022). TD was an adverse indicator in CRC, and the varying number of TDs represented a classified prognostic factor in CRC. TD staging in the TNM 8th might not be reasonable as it ignores the status and the number of TDs.

Overexpression of G-protein-coupled receptors 65 in glioblastoma predicts poor patient prognosis.

OBJECTIVE: G-protein-coupled receptors 65 (GPR65), identified as an acid-sensing receptor, is overexpressed in several malignancies and promote tumor development. Our aim was to investigate the expression and prognostic value of GPR65 in glioblastoma. MATERIALS AND METHODS: We determined the expression of GPR65 protein using immunohistochemistry in tissue microarrays containing 11 Grade I, 107 Grade II, 47 Grade III, and 102 Grade IV gliomas and 16 normal brains. Then we evaluated its association with pathological grades, prognosis, and recurrence. The Cancer Genome Atlas (TCGA) group (N=528) was further employed to examine transcriptional level of GPR65 in glioblastoma and the correlation between GPR65 expression and clinical outcome. RESULTS: In our cohort, GPR65 expression was positively related to glioma pathological grade (p<0.01) and elevated in glioblastoma (p<0.01). High expression of GPR65 was associated with significantly short overall survival (OS) (p=0.013) and progression-free survival (PFS) (p=0.029), and could be identified as an independent risk factor for OS of glioblastoma patients (Hazard Ratio [HR]=1.596, p=0.037). As an aiding evidence, increased GPR65 mRNA expression was also found in TCGA glioblastoma group (p<0.001) and its high level predicted a poor clinical outcome (OS, p=0.003; PFS, p=0.001). CONCLUSION: Our findings suggest that GPR65 is overexpressed in glioblastoma and its high expression predicts unfavorable clinical outcome for patients. Targeting GPR65 may serve as a potential therapy for treating glioblastoma.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging.

BACKGROUND: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. METHODS: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. RESULTS: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. LIMITATIONS: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. CONCLUSION: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.