Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants.

BACKGROUND: Pre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of "hot" or "immune-sensitive" tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs. METHODS: Electronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations. RESULTS: A total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57-0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14-1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56-1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection. CONCLUSIONS: This study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearum.

Histone acetylation, balanced by histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes, affects dynamic transitions of chromatin structure to regulate transcriptional accessibility. However, little is known about the interplay between HAT and HDAC complexes in Fusarium graminearum, a causal agent of Fusarium Head Blight (FHB) that uniquely contains chromosomal regions enriched for house-keeping or infection-related genes. In this study, we identified the ortholog of the human inhibitor of growth (ING1) gene in F. graminearum (FNG1) and found that it specifically interacts with the FgEsa1 HAT of the NuA4 complex. Deletion of FNG1 led to severe growth defects and blocked conidiation, sexual reproduction, DON production, and plant infection. The fng1 mutant was normal in H3 acetylation but significantly reduced in H4 acetylation. A total of 34 spontaneous suppressors of fng1 with faster growth rate were isolated. Most of them were still defective in sexual reproduction and plant infection. Thirty two of them had mutations in orthologs of yeast RPD3, SIN3, and SDS3, three key components of the yeast Rpd3L HDAC complex. Four mutations in these three genes were verified to suppress the defects of fng1 mutant in growth and H4 acetylation. The rest two suppressor strains had a frameshift or nonsense mutation in a glutamine-rich hypothetical protein that may be a novel component of the FgRpd3 HDAC complex in filamentous fungi. FgRpd3, like Fng1, localized in euchromatin. Deletion of FgRPD3 resulted in severe growth defects and elevated H4 acetylation. In contract, the Fgsds3 deletion mutant had only a minor reduction in growth rate but FgSIN3 appeared to be an essential gene. RNA-seq analysis revealed that 48.1% and 54.2% of the genes with altered expression levels in the fng1 mutant were recovered to normal expression levels in two suppressor strains with mutations in FgRPD3 and FgSDS3, respectively. Taken together, our data showed that Fng1 is important for H4 acetylation as a component of the NuA4 complex and functionally related to the FgRpd3 HDAC complex for transcriptional regulation of genes important for growth, conidiation, sexual reproduction, and plant infection in F. graminearum.

Direct electrochemical generation of supercooled sulfur microdroplets well below their melting temperature.

Supercooled liquid sulfur microdroplets were directly generated from polysulfide electrochemical oxidation on various metal-containing electrodes. The sulfur droplets remain liquid at 155 °C below sulfur's melting point (Tm = 115 °C), with fractional supercooling change (Tm - Tsc)/Tm larger than 0.40. In operando light microscopy captured the rapid merging and shape relaxation of sulfur droplets, indicating their liquid nature. Micropatterned electrode and electrochemical current allow precise control of the location and size of supercooled microdroplets, respectively. Using this platform, we initiated and observed the rapid solidification of supercooled sulfur microdroplets upon crystalline sulfur touching, which confirms supercooled sulfur's metastability at room temperature. In addition, the formation of liquid sulfur in electrochemical cell enriches lithium-sulfur-electrolyte phase diagram and potentially may create new opportunities for high-energy Li-S batteries.

Effects of dendrobium polysaccharides on human brain microvascular endothelial cell injury induced by ox-LDL via regulating the miR-378 expression.

Brain microvascular endothelial cells are a key part of the blood-brain barrier. This experiment was set up to investigate the effect and molecular mechanism of Dendrobium polysaccharide on oxidized low-density lipoprotein (ox-LDL)-induced damage to the human brain microvascular endothelial cells. For this purpose, human brain microvascular endothelial cells HBMEC were divided into control group (without any treatment), ox-LDL group (50 µg/mL ox-LDL), Dendrobium polysaccharide low, medium and high concentration group (0.1 µg/L, 0.2 µg/L, 0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL), ox-LDL+miR-NC group (transfection miR-378 mimic negative control+50 µg/mL ox-LDL), ox-LDL+miR-378 group (transfected miR-378 mimics+50 µg/mL ox-LDL), ox-LDL+DP+anti-miR-NC group (transfected miR-378 inhibitor negative control +0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL), ox-LDL+DP+anti-miR-378 group (transfected miR-378 inhibitor+0.4 µg/L Dendrobium polysaccharide+50 µg/mL ox-LDL ). The kit was used to detect the levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT); flow cytometry to detect apoptosis; and Western blot to detect B-cell lymph tumor/leukemia-2 (Bcl-2) and Bcl-2 related X (Bax) protein expression; real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-378. Results showed that after treatment with different concentrations of Dendrobium polysaccharides, MDA levels were decreased in ox-LDL-induced human brain microvascular endothelial cells, SOD and CAT activities were increased, apoptosis rate was decreased, Bcl-2 expression was increased, Bax expression was decreased, miR-378 expression was increased, in a dose-dependent manner (P<0.05). Overexpression of miR-378 inhibits ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells. Inhibition of miR-378 expression reversed the effect of Dendrobium polysaccharide on ox-LDL-induced damage to human brain microvascular endothelial cells. Then dendrobium polysaccharide may inhibit ox-LDL-induced oxidative stress and apoptosis in human brain microvascular endothelial cells by up-regulating the expression of miR-378.

A Two-Dimensional MoS2 Catalysis Transistor by Solid-State Ion Gating Manipulation and Adjustment (SIGMA).

A variety of methods including tuning chemical compositions, structures, crystallinity, defects and strain, and electrochemical intercalation have been demonstrated to enhance the catalytic activity. However, none of these tuning methods provide direct dynamical control during catalytic reactions. Here we propose a new method to tune the activity of catalysts through solid-state ion gating manipulation and adjustment (SIGMA) using a catalysis transistor. SIGMA can electrostatically dope the surface of catalysts with a high electron concentration over 5 × 1013 cm-2 and thus modulate both the chemical potential of the reaction intermediates and their electrical conductivity. The hydrogen evolution reaction (HER) on both pristine and defective MoS2 were investigated as model reactions. Our theoretical and experimental results show that the overpotential at 10 mA/cm2 and Tafel slope can be in situ, continuously, dynamically, and reversibly tuned over 100 mV and around 100 mV/dec, respectively.

Cone-beam computed tomography for evaluating root length of maxillary and mandibular anterior teeth in open bite patients. / 锥形束CT评估前牙开 æ‚£è€ ä¸Šä¸‹é¢Œå‰ç‰™æ ¹é•¿.

OBJECTIVES: To compare the root length of maxillary and mandibular anterior teeth between open bite patients and normal overbite patients via cone-beam computed tomography (CBCT) as well as the root length of anterior teeth in different degree of open bite patients, and to analyze the correlation between the degree of open bite and root length. METHODS: A total of 106 untreated patients were enrolled retrospectively (53 anterior open bite patients and 53 normal overbite patients).Three-dimensional position of the CBCT image for the patient's teeth was performed using Dolphin software. The median sagittal plane of the tooth was used as the measurement plane, and the line connecting the apical point and the midpoint between the labial and lingual cementoenamel junctions was defined as the root length. Independent t-test was used to compare the difference of anterior root length between the open bite group and normal overbite group, mild open bite group and moderate-severe open bite group. Pearson correlation analysis was used to explore the correlation between the degree of open bite and the root length of anterior teeth. RESULTS: Significant differences were found in the root length of maxillary and mandibular anterior teeth between the open bite group and the normal overbite group (P<0.001), and there was significant difference in root length of mandibular central incisor between mild open bite group and moderate-severe open bite group (P=0.039). Pearson correlation analysis showed that maxillary anterior teeth were correlated with root length of anterior teeth (all P<0.05). CONCLUSIONS: The root length of maxillary and mandibular anterior teeth in the open bite patients is shorter than that in the normal overbite patients, and the severer the degree of open bite, the shorter the root length of the mandibular central incisor tends to be. There is a certain relationship between maxillary anterior teeth and the root length of anterior teeth.

Comparative acetylome analysis reveals the potential roles of lysine acetylation for DON biosynthesis in Fusarium graminearum.

BACKGROUND: Fusarium graminearum is a destructive fungal pathogen of wheat, barley and other small grain cereals. During plant infection, the pathogen produces trichothecene mycotoxin deoxynivalenol (DON), which is harmful to human and livestock. FgGCN5 encodes a GCN5 acetyltransferase. The gene deletion mutant Fggcn5 failed to produce DON. We assumed that lysine acetylation might play a key regulatory role in DON biosynthesis in the fungus. RESULTS: In this study, the acetylome comparison between Fggcn5 mutant and wild-type strain PH-1 was performed by using affinity enrichment and high resolution LC-MS/MS analysis. Totally, 1875 acetylated proteins were identified in Fggcn5 mutant and PH-1. Among them, 224 and 267 acetylated proteins were identified exclusively in Fggcn5 mutant and PH-1, respectively. Moreover, 95 differentially acetylated proteins were detected at a significantly different level in the gene deletion mutant:43 were up-regulated and 52 were down-regulated. GO enrichment and KEGG-pathways enrichment analyses revealed that acetylation plays a key role in metabolism process in F. graminearum. CONCLUSIONS: Seeing that the gens playing critical roles in DON biosynthesis either in Fggcn5 mutant or PH-1. Therefore, we can draw the conclusion that the regulatory roles of lysine acetylation in DON biosynthesis in F. graminearum results from the positive and negative regulation of the related genes. The study would be a foundation to insight into the regulatory mechanism of lysine acetylation on DON biosynthesis.

The tri-snRNP specific protein FgSnu66 is functionally related to FgPrp4 kinase in Fusarium graminearum.

Deletion of Prp4, the only kinase among spliceosome components, is not lethal in Fusarium graminearum but Fgprp4 mutants have severe growth defects and produced spontaneous suppressors. To identify novel suppressor mutations of Fgprp4, we sequenced the genome of suppressor S37 that was normal in growth but only partially recovered for intron splicing and identified a tandem duplication of 9-aa in the tri-snRNP component FgSNU66. Among the 19 additional suppressor strains found to have mutations in FgSNU66 (out of 260 screened), five had the same 9-aa duplication event with S37 and another five had the R477H/C mutation. The rest had nonsense or G-to-D mutations in the C-terminal 27-aa (CT27) region of FgSnu66, which is absent in its yeast ortholog. Truncation of this C-terminal region reduced the interaction of FgSnu66 with FgHub1 but increased its interaction with FgPrp8 and FgPrp6. Five phosphorylation sites were identified in FgSnu66 by phosphoproteomic analysis and the T418A-S420A-S422A mutation was shown to reduce virulence. Overall, our results showed that mutations in FgSNU66 can suppress deletion of Fgprp4, which has not been reported in other organisms, and the C-terminal tail of FgSnu66 plays a role in its interaction with key tri-snRNP components during spliceosome activation.

Gate-Induced Metal-Insulator Transition in MoS2 by Solid Superionic Conductor LaF3.

Electric-double-layer (EDL) gating with liquid electrolyte has been a powerful tool widely used to explore emerging interfacial electronic phenomena. Due to the large EDL capacitance, a high carrier density up to 1014 cm-2 can be induced, directly leading to the realization of field-induced insulator to metal (or superconductor) transition. However, the liquid nature of the electrolyte has created technical issues including possible side electrochemical reactions or intercalation, and the potential for huge strain at the interface during cooling. In addition, the liquid coverage of active devices also makes many surface characterizations and in situ measurements challenging. Here, we demonstrate an all solid-state EDL device based on a solid superionic conductor LaF3, which can be used as both a substrate and a fluorine ionic gate dielectric to achieve a wide tunability of carrier density without the issues of strain or electrochemical reactions and can expose the active device surface for external access. Based on LaF3 EDL transistors (EDLTs), we observe the metal-insulator transition in MoS2. Interestingly, the well-defined crystal lattice provides a more uniform potential distribution in the substrate, resulting in less interface electron scattering and therefore a higher mobility in MoS2 transistors. This result shows the powerful gating capability of LaF3 solid electrolyte for new possibilities of novel interfacial electronic phenomena.

Sexual specific functions of Tub1 beta-tubulins require stage-specific RNA processing and expression in Fusarium graminearum.

The wheat head blight fungus Fusarium graminearum has two highly similar beta-tubulin genes with overlapping functions during vegetative growth but only TUB1 is important for sexual reproduction. To better understand their functional divergence during ascosporogenesis, in this study we characterized the sequence elements important for stage-specific functions of TUB1. Deletion of TUB1 blocked the late but not initial stages of perithecium formation. Perithecia formed by tub1 mutant had limited ascogenous hyphae and failed to develop asci. Silencing of TUB1 by MSUD also resulted in defects in ascospore formation. Interestingly, the 3'-UTR of TUB1 was dispensable for growth but essential for its function during sexual reproduction. RIP mutations that specifically affected Tub1 functions during sexual reproduction also were identified in two ascospore progeny. Furthermore, site-directed mutagenesis showed that whereas the non-editable mutations at three A-to-I RNA editing sites had no effects, the N347D (not T362D or I368V) edited mutation affected ascospore development. In addition, the F167Y, but not E198K or F200Y, mutation in TUB1 conferred tolerance to carbendazim and caused a minor defect in sexual reproduction. Taken together, our data indicate TUB1 plays an essential role in ascosporogenesis and sexual-specific functions of TUB1 require stage-specific RNA processing and Tub1 expression.

TRI6 and TRI10 play different roles in the regulation of deoxynivalenol (DON) production by cAMP signalling in Fusarium graminearum.

The biosynthesis of mycotoxin deoxynivalenol (DON) in Fusarium graminearum is regulated by two pathway-specific transcription factors Tri6 and Tri10 and affected by various host and environmental factors. In this study, we showed that cyclic adenosine monophosphate (cAMP) treatment induced DON production by stimulating TRI gene expression and DON-associated cellular differentiation in F. graminearum. Interestingly, exogenous cAMP had no effects on the tri6 mutant but partially recovered the defect of tri10 mutant in DON biosynthesis. Although the two cAMP phosphodiesterase genes PDE1 and PDE2 had overlapping functions in vegetative growth, conidiation, sexual reproduction and plant infection, deletion of PDE2 but not PDE1 activated intracellular PKA activities and increased DON production. Whereas the tri6 pde2 mutant failed to produce DON, the tri10 pde2 double mutant produced a significantly higher level of DON than the tri10 mutant. Cellular differentiation associated with DON production was stimulated by exogenous cAMP or deletion of PDE2 in both tri10 and tri6 mutants. These data indicate that TRI6 is essential for the regulation of DON biosynthesis by cAMP signalling but elevated PKA activities could partially bypass the requirement of TRI10 for TRI gene-expression and DON production, and Pde2 is the major cAMP phosphodiesterase to negatively regulate DON biosynthesis in F. graminearum.

Acupuncture and moxibustion treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is a common autoimmune disease that often involves the skeletal muscle of the whole body and seriously affects patients' quality of life. Acupuncture and moxibustion treatment of MG has unique advantages, the aim is to evaluate the clinical effect of acupuncture and moxibustion on MG. METHODS: The literature on acupuncture and moxibustion treating MG in PubMed, CochraneLibrary, EMBASE, SCI, China Academic Journals full-text database, China Biology Medicine disc, VIP and Wanfang database were searched through computers from the establishment of the database to December 2022. RESULTS: A total of 11 studies were included, involving 658 patients, where 330 in the treatment group and 328 in the control group. The results of the meta-analysis showed that the treatment group performed better than the control group in improving the total clinical response rate (OR = 3.26, 95%[2.04,5.21], P < .01). Additionally, the treatment group outperformed the control group in raising the absolute clinical score (MD = -3.48, 95%CI[-5.17, -1.78], P < .01). However, there was no significant difference between the treatment group and the control group in improving the level of serum interleukin-6 receptor (MD = -1.45,95%CI[-6.85,3.95], P > .05) and OMG quantitative score (MD = -2.16,95%CI[-4.85,0.52], P > .05). The total clinical effective rate was tested for publication bias, which showed that the 2 sides of the funnel plot were asymmetrical, suggesting the possible existence of publication bias. CONCLUSION: Acupuncture and moxibustion has a good effect on MG, which is better than conventional Western medicine in improving the total clinical effective rate and absolute clinical score.

The interaction effect of depressive symptoms and inflammation on the occurrence of cardiovascular diseases.

BACKGROUND: Whether there was an interaction effect between depressive symptoms and inflammation on the occurrence of cardiovascular diseases (CVDs) was unclear. METHODS: In this cross-sectional study, 3346 participants in the National Health and Nutrition Examination Survey (NHANES) were included. Multivariable regression analysis was performed to explore the associations of depressive symptoms or inflammation with CVDs. The attributable proportion of interaction (API), and synergy index (SI) were applied for evaluating the statistical significance of the interaction effect. RESULTS: Depressive symptoms were associated with 2.31-fold risk of CVDs [odds ratio (OR) = 2.31, 95 % confidence interval (CI): 1.47-3.62). The increased risk of CVDs was observed in people with neutrophil to lymphocyte ratio (NLR) ≥1.88 group (OR = 1.36, 95%CI: 1.01-1.85) and neutrophil/[white blood cell (WBC)-neutrophil] ≥1.35 (OR = 1.52, 95%CI: 1.12-2.07) after adjusting for confounders. The interaction effect of depressive symptoms and high NLR on the risk of CVDs was statistically significant with an OR value of 2.60 (95%CI: 1.43-4.70) compared to low NLR and no depressive symptoms group after adjusting for confounders. The API was 0.66 (95%CI: 0.44-0.89) and SI was 4.23 (95%CI: 2.08-8.59). The interaction effect of depressive symptoms and high neutrophil/(WBC-neutrophil) was associated with the risk of CVDs compared to low neutrophil/(WBC-neutrophil) and no depressive symptoms group (OR = 3.59, 95%CI: 2.00-6.45). The API was 0.78 (95%CI: 0.63-0.93) and SI was 6.75 (95%CI: 3.55-12.82). CONCLUSION: There was an interaction effect of depressive symptoms and inflammation on the occurrence of CVDs.

Efficacy and Safety of Immune Checkpoint Inhibitors in Triple-negative Breast Cancer: A Study Based on 41 Cohorts Incorporating 6558 Participants.

The project was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC). Electronic databases were screened to identify relevant trials. The primary endpoints were prognostic parameters and adverse events (AEs) through pooled rate, odds ratio, and hazard ratio (HR) with 95% CI. Totally, 6558 TNBC patients from 41 cohorts were included. The pooled pathologic complete response rate (odds ratio=2.03, 95% CI: 1.35-3.06, P =0.0007) and event-free survival (HR=0.84, 95% CI: 0.73-0.96, P =0.0100) of ICIs plus chemotherapy was higher than that of chemotherapy-alone in early-stage TNBC. For metastatic TNBC, compared with chemotherapy-alone, the addition of ICIs prolonged the progression-free survival (PFS) (HR=0.92, 95% CI: 0.88-0.96, P <0.0001); the improvement also existed in the following 3 subgroups: programmed cell death-ligand 1 positive, race of White and Asian, and patients without previous neoadjuvant or adjuvant chemotherapy; however, the benefit of the combined regimen was not observed in overall survival (OS) (HR=0.95; 95% CI: 0.89-1.03, P =0.2127). In addition, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone. In the safety analysis, compared with chemotherapy-alone, ICIs plus chemotherapy increased immune-related AEs and several serious AE. The regimen of ICIs plus chemotherapy is promising in both early-stage and metastatic TNBC, while the increased serious AE should not be neglected. Furthermore, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone.

Impact of probiotics use on clinical outcomes of immune checkpoint inhibitors therapy in cancer patients.

BACKGROUND: Dysbiosis of the gut microbiota can lead to impaired therapeutic effect of immune checkpoint inhibitors (ICIs). This study aimed to investigate the use of probiotics on the clinical outcomes of cancer patients receiving ICIs therapy. METHOD: PubMed, EMBASE, and the Cochrane Library database were searched to retrieve relevant studies that exploring the relationship between probiotics and the efficacy of ICIs. The primary endpoints included overall survival (OS) and progression-free survival (PFS), evaluated by the hazard rations (HRs) with 95% confidence intervals (CI), and the secondary endpoint was objective response rate (ORR), evaluated by the odd ratio (OR) with a 95% CI. RESULTS: A total of five studies including 1031 patients were eligible for analysis. Our results indicated that the use of probiotics was associated with a superior OS (HR = 0.50, 95% CI: 0.30-0.85, p = 0.01) and PFS (HR = 0.51, 95% CI: 0.42-0.61, p < 0.01), but had no relationship with ORR (OR = 2.11, 95%CI: 0.51-8.65, p = 0.30) in non-small cell lung cancer (NSCLC) patients. CONCLUSIONS: Probiotics were positively correlated with OS and PFS in NSCLC patients administrated with ICIs, but had no relationship with ORR.

Effect of comprehensive nursing on patients with chalazion undergoing intense pulsed light and its influence on postoperative recurrence.

OBJECTIVE: To explore the effect of comprehensive nursing on patients with chalazion undergoing intense pulsed light (IPL) and its influence on postoperative recurrence. METHODS: In this retrospective study, the medical records of 72 patients who received IPL treatment for chalazion from October 2021 to February 2023 were analyzed. Among them, 33 patients treated with comprehensive nursing were included in the research group (RG) and 39 patients treated with routine nursing were included in the control group (CG). The treatment effect, complications and recurrence were compared between the two groups. The psychological state of patients and their satisfaction about the nursing were recorded and compared between the two groups. RESULTS: After nursing, the severity of unhealthy emotion in the RG was obviously better than that in the CG (P=0.033); The overall response rate in the RG was obviously higher than that in the CG (P=0.035). The nursing satisfaction in RG was significantly higher than that in the CG (P=0.035). The incidence of complications in RG was obviously lower than that in the CG (P=0.045). CONCLUSION: Comprehensive nursing is effective in improving the therapeutic effect and reducing the postoperative recurrence rate for patients with chalazion.

[Study on the effect of alginate impression spray disinfection process on model accuracy].

PURPOSE: To investigate the effect of a new cleaning and disinfection process of oral impressions on the accuracy of alginate dental impression. METHODS: Sixteen young volunteers were selected to make alginate oral impression (2 times for each upper and lower jaw) and oral scandata acquisition (1 time for each upper and lower jaw) to obtain STL data. The 2 pairs of alginate impressions of each subject were numbered group 1, group 2, inwhich group 1 was not sterilized and the oral impression film in group 2 was treated with the method and steps of new oral impression cleaning and disinfection. All the oral impressions of the subjects were perfused with plaster models in the same standard way and demoulded. The obtained plaster models were examined and scanned after appropriate trimming and grinding. The plaster model data obtained from each group of each patient after warehouse scanning were compared with the orally scanned model data for alignment analysis, and root mean square(RMS) was used as a parameter to evaluate the deviation between the test model and the standard model. The chromatograms of the deviations were saved for visualization and analysis to observe the differences in model accuracy from several dimensions. Statistical analysis was performed with SPSS 23.0 software package. RESULTS: The differences in RMS of model accuracy of maxillary dental series of alginate impressions were statistically significant, in which the RMS of the group disinfecting the maxillary oral impression film with a new oral impression cleaning and disinfection process was significantly higher than that of the nonsterilized group (P=0.006), while the difference between model accuracy RMS of the mandibular disinfection group and non-disinfection group was not statistically significant(P=0.874). CONCLUSIONS: The new technical specifications for cleaning and disinfection of dental impressions recommended by the Chinese Stomatological Association have certain effects on the accuracy of dental impressions made of alginate material,and the details in its process should be further improved.

IL-23/IL-17 immune axis mediates the imiquimod-induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF-κB pathway in macrophages and keratinocytes.

The interleukin-23 (IL-23)/IL-17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL-23/IL-17 immune axis in the serum of patients with psoriasis using enzyme-linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti-IL-23A or anti-IL-17A antibodies for 7 days. The potential effects of the IL-23/IL-17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin-eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF-κB, and pNF-κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL-23/IL-17 immune axis: IL-2, IL-4, IL-8, IL-12, IL-17, IL-22, IL-23, and interferon-γ. Levels of IL-23p19 and IL-17 were increased in serum and skin of IMQ-treated mice, while ACT1, TRAF6, TAK1, NF-κB, and pNF-κB were upregulated in the skin. A large proportion of NF-κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti-IL-23 or anti-IL-17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF-κB, and pNF-κB in skin. Our results suggest that skin inflammation mediated by the IL-23/IL-17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF-κB pathway in keratinocytes and macrophage.

Prognostic Value of Lymphocyte-to-Monocyte Ratio (LMR) in Cancer Patients Undergoing Immune Checkpoint Inhibitors.

Background: There is accumulating evidence that the lymphocyte-to-monocyte ratio (LMR) is related to the outcomes of cancer patients treated with immune checkpoint inhibitors (ICIs). However, the results remain controversial. Method: Electronic databases were searched to retrieve the studies that explore the relationship between LMR and the efficacy of ICIs. The primary endpoints were overall survival (OS) and progression-free survival (PFS), evaluated by the hazard ratios (HRs) with 95% confidence intervals (CI), and the secondary endpoints included disease control rate (DCR) and immune-related adverse events (irAEs), assessed by the odd ratios (ORs) with 95% CI. Results: A total of 27 studies involving 4,322 patients were eligible for analysis. The results indicated that increased LMR at baseline was associated with a superior OS (HR: 0.46, 95% CI: 0.39-0.56, p < 0.001), PFS (HR: 0.60, 95% CI: 0.49-0.74, p < 0.001), and DCR (OR: 3.16, 95% CI: 1.70-5.87, p < 0.001). Posttreatment LMR was linked to a better PFS (HR: 0.46, 95% CI: 0.29-0.71, p = 0.001), but failed to show this correlation in the analysis of OS and DCR. No correlation existed between LMR and irAEs regardless of the testing time (baseline or posttreatment). Subgroup analyses focusing on baseline LMR revealed that higher baseline LMR possessed a better OS in renal cell cancer (RCC) arm, nonsmall cell lung cancer (NSCLC) arm, multiple cancer arm, monotherapy arm, LMR <2 arm, LMR ≥2 arm, western countries arm, eastern countries arm, and anti-PD-1 arm. Higher baseline LMR correlated with better PFS in RCC arm, NSCLC arm, gastric cancer (GC) arm, multiple cancer arm, LMR <2 arm, LMR ≥2 arm, western countries arm, and eastern countries arm. Conclusions: Higher LMR at baseline was positively correlated with a superior OS, PFS, and DCR for ICIs, but not with irAEs.

The safety and efficacy of immune-checkpoint inhibitors in patients with cancer and pre-existing autoimmune diseases.

Objective: This study aims at investigating the safety and efficacy of immune-checkpoint inhibitors (ICIs) in patients with cancer and pre-existing autoimmune disease (AID). Materials & methods: PubMed, Embase and Cochrane Library were searched for relevant studies. The primary end points of the study were immunotoxicity and cancer response. Results: At the early use of ICIs, compared with those with active AID, grade 3-4 AID flare occurred more frequently in patients with inactive AID after treatment with ICIs; and the incidence of grade 3-4 immunotoxic effects was significantly lower in patients undergoing immunosuppressive therapy than those without corresponding treatment. In addition, patients with worsening AID generally obtained a better objective response than those without a flare. Conclusion: This study demonstrates that the toxic effects induced by immunotherapy are generally manageable in patients with cancer and pre-existing AID, some of whom even achieve satisfactory antitumor effects in clinical practice.