The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.

Mediating the Role of Perceived Social Support Between Frailty and Self-Perceived Burden in Elderly Patients with Diabetes.

Objective: To explore the mediating effects of perceived social support between frailty and self-perceived burden (SPB) in elderly patients with diabetes and to provide a theoretical basis for reducing that burden. Methods: A total of 169 elderly patients with diabetes who were hospitalised in the endocrinology department of a third-class hospital in Wuxi between May 2020 and July 2022 were included in this study using the convenience sampling method. Patients were assessed by the general information questionnaire, the Chinese version of the Tilburg frailty inventory (TFI), the Self-Perceived Burden Scale (SPBS) and the Perceived Social Support Scale (PSSS). The SPSS 22.0 software was used for Pearson's correlation analysis and multiple linear regression analysis. Model four of the SPSS PROCESS was used for mediating the effect analysis. Results: The SPBS of elderly patients with diabetes was positively correlated with the TFI (P < 0.01) and negatively correlated with the PSSS (P < 0.01). The results of the Bootstrap test showed that the mediating effect of the PSSS on the relationship between the TFI and the SPBS in elderly patients with diabetes was 0.296 (95% CI: 0.007, 0.066), and the mesomeric effect accounted for 17.3% of the total effect. Conclusion: The debilitation of elderly patients with diabetes can be reduced by decreasing their SPB through perceived social support. This can be achieved through comprehensive interventions by nurses.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

OBJECTIVES: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity. METHODS: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m2. The hazard ratio (HR) for death was calculated using Cox regression analysis. RESULTS: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013). CONCLUSION: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay.

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.

High albumin-bilirubin grade predicts worse short-term complications in gastric cancer patients with metabolic syndrome: a retrospective study.

Background: Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). Methods: There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Results: Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). Conclusions: The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.

MHC class II regulation of CD8+ T cell tolerance and implications in autoimmunity and cancer immunotherapy.

Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.

Integration of Protein Nanocage with CpG Motifs: A Virus-Mimicked Core-Shell Nanostructure to Ignite Antitumor Immunity.

The tumor microenvironment typically possesses immunosuppressive properties that hinder the effectiveness of antitumor immune responses, even in the context of immunotherapies. However, it is observed that pathogenic microorganisms can trigger strong immune responses during infection, offering a potential means to counteract the immunosuppressive environment of tumors. In this study, a protein nanocage called CpG@HBc nanocages (NCs) is developed, which mimics the structure of the hepatitis B virus and combines with an immunostimulatory component known as cytosine phosphoguanosine oligonucleotide (CpG). By delivering these immunostimulatory agents, CpG@HBc NCs are able to effectively reverse the suppressive tumor microenvironment, resulting in the inhibition of poorly immunogenic tumors in mice. Through high-dimensional mass cytometry (CyTOF) analysis, remarkable alterations in immune responses is observed induced by CpG@HBc. Treatment with immunogenic CpG@HBc NCs, along with co-injection of an OX40 agonist, sensitized colorectal cancer tumors to T cell immune responses, resulting in significant impairment of tumor growth and robust immune activation. Furthermore, CpG@HBc NCs induced long-term antitumor immunological memory, protecting tumor-cured mice from tumor rechallenge. Overall, these findings highlight the potential of a virus-inspired protein nanocage to mimic anti-viral immunity and offer a unique therapeutic approach for cancer immunotherapy.

TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.

Themis suppresses the effector function of CD8+ T cells in acute viral infection.

CD8+ T cells play a central role in antiviral immune responses. Upon infection, naive CD8+ T cells differentiate into effector cells to eliminate virus-infected cells, and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved. Although extensively investigated, the underlying mechanisms of CD8+ T-cell differentiation remain incompletely understood. Themis is a T-cell-specific protein that plays critical roles in T-cell development. Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8+ T-cell homeostasis, cytokine responsiveness, and antibacterial responses. In this study, we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection. We found that preexisting CD8+ T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice. Further analyses showed that in the primary immune response, Themis deficiency promoted the differentiation of CD8+ effector cells and increased their TNF and IFNγ production. Moreover, Themis deficiency impaired memory precursor cell (MPEC) differentiation but promoted short-lived effector cell (SLEC) differentiation. Themis deficiency also enhanced effector cytokine production in memory CD8+ T cells while impairing central memory CD8+ T-cell formation. Mechanistically, we found that Themis mediates PD-1 expression and its signaling in effector CD8+ T cells, which explains the elevated cytokine production in these cells when Themis is disrupted.

Analysis of Expression of Inflammatory Factors and T Cell Lymphocyte in Patients with Orthopedic Trauma after Infection and Risk Factors.

Since most orthopedic patients' wounds are open in clinical practice, postoperative wound infection and other conditions are prone to occur, which pose varying degrees of threat to patients' prognosis and life and health. In this paper, a retrospective study is conducted on orthopedic trauma patients in our hospital from January 2020 to January 2022, including 98 patients with postoperative infection and 98 patients without infection, to detect and compare the levels of inflammatory factors and the level of T cell lymphatic group index difference. The ROC curve is drawn to analyze the diagnostic efficacy of postoperative infection indicators for patients with orthopedic trauma. The differences in baseline data between the two groups are compared. Multivariate Logistic regression analysis is performed on infection status. The experimental results show that the IL-6, IL-2, and CRP of the infection group of patients are significantly higher than uninfected group, and the CD3, CD4, and CD8 are significantly lower than uninfected group, which means that patients with infection after orthopedic trauma are in a disordered state of immune cytokines and function. Therefore, postoperative infection can be effectively assessed by early combined detection of the above indicators. In addition, the analysis of other clinical data showed that the operation time, the number of underlying diseases, and the surgical method are also risk factors for postoperative infection.

[Microbial Community Structure of Activated Sludge for Total Nitrogen Upgrading Project].

The activated sludge of a biochemical unit (WLK_OD) and an advanced denitrification unit (WLK_AD) were collected from a municipal wastewater treatment plant (WWTP), in which the TN concentration of effluent was less than 1.5 mg·L-1, and their microbial community structure and function profiles were analyzed using 16S rRNA gene high-throughput sequencing. The microorganisms in WLK_AD had lower evenness compared with that in WLK_OD, which was attributed to environmental selection. Furthermore, PCoA revealed that different incoming wastewaters had an impact on microbial community structure. At the phylum level, Proteobacteria (70.11%) was enriched in WLK_AD. At the genus level, Thauera, Flavobacterium, Hydrogenophaga, and Zoogloea served as distinct-dominant denitrifying bacteria in WLK_AD; however, Trichococcus (3.50%) and Terrimonas (1.10%) were enriched in WLK_OD. Through the comparison between groups (P<0.05), the biomarkers detected in each WWTP were different. Furthermore, the results of the co-occurrence network showed that the bacteria from module I had a higher proportion in WLK_AD; the bacteria from module II had a higher proportion in WLK_OD, and they were common microorganisms in WWTPs, implying that wastewater environments drpve the differences in the microbial community structure. Among the types of environmental parameters, the removal efficiency of COD and TN had the greatest impact on the microbial community by the RDA. The removal efficiency of COD was positively correlated with the dominant bacteria from WLK_OD, such as Saccharibacteria, Thermomarinilinea, Terrimonas, and Comamonas; the removal efficiency of TN was positively correlated with the denitrifying bacteria from WLK_AD, such as Dokdonella, Thauera, Flavobacterium, and Zoogloea. WLK_AD was enriched with Novosphingobium, Dokdonella, Thauera, and Sphingomonas, which synergistically removed TN, leading to the TN of the effluent being less than 1.5 mg·L-1. Moreover, based on the results of function prediction, WLK_AD had a higher proportion of genes that could code the denitrification enzymes.

Resection of Insular Glioma Through the Transfrontal Limiting Sulcus Approach.

BACKGROUND: The current transsylvian or transopercular approaches make access difficult because of the limited exposure of insular tumors. Hence, maximal and safe removal of insular gliomas is challenging. In this article, a new approach to resect insular gliomas is presented. OBJECTIVE: To determine whether the new transfrontal limiting sulcus approach is helpful for maximal and safe removal of insular gliomas. METHODS: The authors reported surgical techniques for insular gliomas resected through the transfrontal limiting sulcus approach. The authors evaluated the surgical resections of 69 insular gliomas performed through the new approach in their department. The extents of resection and postoperative neurological outcomes were analyzed to determine the value of this new approach. RESULTS: Based on the Berger-Sanai classification, most insular gliomas were giant tumors (59.42%), followed by zone I + IV tumors (24.64%). The median (interquartile range) extent of resection of all patients was 100% (91%, 100%). The total resection rate for all gliomas was (55 of 69, 79.7%), and the total resection rate for low-grade gliomas was (28 of 40, 70%), which was significantly lower than that for high-grade gliomas (27 of 29, 93.1%) (P = .019). All patients had muscle strength greater than grade 4 3 months after surgery. Only 1 patient had a speech disorder 3 months after surgery. The median Karnofsky Performance Status score at the time of the 3-month follow-up was 90. CONCLUSION: The transfrontal limiting sulcus approach can help to achieve maximal and safe removal of insular gliomas.

Prognostic value of myosteatosis and sarcopenia for elderly patients with colorectal cancer: A large-scale double-center study.

BACKGROUND: Myosteatosis and sarcopenia are forms of muscle depletion that impair the normal physiological function of elderly patients, resulting in a worse prognosis. This study aimed to evaluate the prognostic value of sarcopenia and myosteatosis on postoperative outcomes in elderly patients with colorectal cancer. METHODS: From February 2015 to March 2021, a total of 921 elderly patients who underwent curative surgeries for colorectal cancer at 2 centers were enrolled and grouped by the presence of either myosteatosis or sarcopenia. Clinicopathological characteristics and postoperative outcomes were compared between the 2 groups. The independent risk factors for complications and overall survival were evaluated. RESULTS: Patients with myosteatosis had higher incidences of total and surgical complications, longer surgical duration, lower numbers of lymph nodes harvested, and longer postoperative hospital stays. Patients with sarcopenia had higher incidences of total complications, medical complications, and shorter surgical durations. Both conditions had adverse effects on overall survival and disease-free survival. Overweight status (P = .004), hypoalbuminemia (P < .001), myosteatosis, (P = .029) and sarcopenia (P = .017) were independent risk factors for total complications. Hypoalbuminemia (P = .035), myosteatosis (P = .003), sarcopenia (P = .027), and tumor-nodes-metastasis stage (≥Ⅲ; P < .001) were independent negative prognostic factors for overall survival. CONCLUSION: Myosteatosis and sarcopenia have different characteristics and are associated with poor prognoses in elderly patients with colorectal cancer. Myosteatosis occurs more frequently. Early diagnosis and intervention for myosteatosis should be included in preoperative management, which may improve prognosis in elderly patients.

Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.

The Microbiome of Meibomian Gland Secretions from Patients with Internal Hordeolum Treated with Hypochlorous Acid Eyelid Wipes.

OBJECTIVE: The aims of our experiment were to compare the microorganisms in meibomian gland secretions from patients with internal hordeolum before and after treatment using hypochlorous acid eyelid wipes, to elucidate the mechanism underlying hypochlorous acid eyelid wipe treatment of internal hordeolum. METHODS: This was a prospective, matched-pair study. A total of eight patients with internal hordeolum who attended the ophthalmology clinic of our hospital from April to August 2020 were included. Meibomian gland secretions were collected from subjects before treatment (Group A) and from patients cured after eyelid cleaning with hypochlorous acid eyelid wipes for 7 days (Group B). Samples were submitted to 16S rRNA high-throughput sequencing, and the resulting data were analyzed to compare the differences in the structure and composition of meibomian gland secretion microbial flora before and after treatment of internal hordeolum. RESULTS: A total of 2127 operational taxonomic units were obtained from the two groups of samples, and there was no significant difference in alpha diversity before and after eyelid cleaning. At the phylum level, there was no significant difference between the two groups. The predominant phyla in Group A included the following: Firmicutes (32.78% ± 20.16%), Proteobacteria (26.73% ± 7.49%), Acidobacteria (10.58% ± 11.45%), Bacteroidetes (9.05% ± 6.63%), Actinobacteria (8.48% ±1.77%), and Chloroflexi (3.15% ± 3.12%), while those in Group B were the following: Proteobacteria (31.86% ± 9.69%), Firmicutes (29.07% ± 24.20%), Acidobacteria (11.33% ± 7.53%), Actinobacteria (7.10% ± 1.98%), Bacteroidetes (5.39% ± 5.17%), and Chloroflexi (3.89% ± 3.67%). Starting from the class level, significant differences in microbial communities were detected before and after eyelid cleaning (P < 0.05). Linear discriminant analysis effect size analysis showed the core flora in Group A microbiome comprising Actinobacteria, Staphylococcus, Staphylococcaceae, Staphylococcus aureus, Ruminococcacea UCg-014, Ruminococcacea-UCG-014, Halomonadaceae, Neisseria, Methylobacterium, Frankiales, and Neisseria sicca, while those in Group B microbial were Streptococcus sp., Blautia, Bifidobacterium pseudocatenulatum, Subdoligranulum, Subdoligranulum variabile, Faecalibacterium, and Faecalibacterium prausnitzii. CONCLUSION: Eyelid cleaning with hypochlorous acid eyelid wipes does not change the biodiversity in the meibomian gland secretions of patients with internal hordeolum. Hypochlorous acid eyelid wipes may affect the internal hordeolum through broad-spectrum antibacterial action to effectively reduce the relative abundance of symbiotic pathogens, such as Staphylococcus, Neisseria, Actinomycetes, and Ruminococcus and increase that of Faecalibacterium prausnitzii and other symbiotic probiotics with anti-inflammatory effects.

Global leadership initiative in malnutrition (GLIM) criteria using hand-grip strength adequately predicts postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer.

BACKGROUND: The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI). METHODS: Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS. RESULTS: A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P < 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P < 0.001, both), and disease-free survival (P < 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications. CONCLUSIONS: GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.

Themis is indispensable for IL-2 and IL-15 signaling in T cells.

To perform their antiviral and antitumor functions, T cells must integrate signals both from the T cell receptor (TCR), which instruct the cell to remain quiescent or become activated, and from cytokines that guide cellular proliferation and differentiation. In mature CD8+ T cells, Themis has been implicated in integrating TCR and cytokine signals. We investigated whether Themis plays a direct role in cytokine signaling in mature T cells. Themis was required for IL-2- and IL-15-driven CD8+ T cell proliferation both in mice and in vitro. Mechanistically, we found that Themis promoted the activation of the transcription factor Stat and mechanistic target of rapamycin signaling downstream of cytokine receptors. Metabolomics and stable isotope tracing analyses revealed that Themis deficiency reduced glycolysis and serine and nucleotide biosynthesis, demonstrating a receptor-proximal requirement for Themis in triggering the metabolic changes that enable T cell proliferation. The cellular, metabolic, and biochemical defects caused by Themis deficiency were corrected in mice lacking both Themis and the phosphatase Shp1, suggesting that Themis mediates IL-2 and IL-15 receptor-proximal signaling by restraining the activity of Shp1. Together, these results not only shed light on the mechanisms of cytokine signaling but also provide new clues on manipulating T cells for clinical applications.

Effect of GLIM-defined malnutrition on postoperative clinical outcomes in patients with colorectal cancer.

BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.