High-Throughput Antigen Microarray Identifies Longitudinal Prognostic Autoantibody for Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer.

Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.

Efficacy of dolutegravir + lamivudine q.d. with food in people with TB/HIV using a rifampicin-based regimen: A retrospective observational case series.

OBJECTIVES: Dolutegravir + lamivudine (DTG + 3TC) is a first-line regimen for people with HIV. However, there are still concerns about its efficacy in people with tuberculosis (TB)/HIV due to the lack of available evidence and drug-drug interaction with rifampicin. METHODS: A single-centre retrospective observational case series was conducted in Guangxi Zhuang Autonomous Region, China. We included all people with TB/HIV on combined use of once-daily (q.d.) dosing DTG + 3TC and rifampicin (RIF)-containing anti-TB regimens between 2020 and 2022. HIV-RNA, CD4 cell counts were collected and analysed. RESULTS: In all, 21 people with HIV (PWH) were included in this study. All the PWH were treatment-naïve and told to take DTG + 3TC q.d. with food. The median age was 53 years, and 71.43% were male. A total of 71.43% PWH had baseline viral load (VL) > 100 000 copies/mL, and 33.33% had baseline VL greater than 500 000 copies/mL. Only one PWH had CD4 cell count greater than 200 cells/µL, and the median CD4 count was 20 cells/µL. A total of 16 PWH started DTG + 3TC after initiation of the RIF-based anti-TB regimen, and the other five PWH initiated DTG + 3TC before the treatment of TB. All the PWH had at least 24 weeks of follow-up visits and all of the TB treatments were successful. A total of 20 PWH (95.24%) achieved viral suppression (VL <50 copies/mL). All detected viral loads between weeks 24 and 48 were less than 200 copies/mL. Among the PWH who started DTG + 3TC after the initiation of RIF-based anti-TB regimen, all achieved viral suppression by week 24 except the non-suppressed PWH. CD4 counts were greatly improved after antiretroviral treatment: the median CD4 counts were raised from 20 to 171 cells/µL at week 48. No serious adverse events were reported. CONCLUSIONS: This case series preliminarily validates the efficacy of DTG + 3TC q.d. with food when combined with RIF-based anti-TB regimens in people with TB/HIV.

Glutathione depletion and dihydroorotate dehydrogenase inhibition actuated ferroptosis-augment to surmount triple-negative breast cancer.

Ferroptosis is a promising therapeutic approach for combating malignant cancers, but its effectiveness is limited in clinical due to the adaptability and self-repair abilities of cancer cells. Mitochondria, as the pivotal player in ferroptosis, exhibit tremendous therapeutic potential by targeting the intramitochondrial anti-ferroptotic pathway mediated by dihydroorotate dehydrogenase (DHODH). In this study, an albumin-based nanomedicine was developed to induce augmented ferroptosis in triple-negative breast cancer (TNBC) by depleting glutathione (GSH) and inhibiting DHODH activity. The nanomedicine (ATO/SRF@BSA) was developed by loading sorafenib (SRF) and atovaquone (ATO) into bovine serum albumin (BSA). SRF is an FDA-approved ferroptosis inducer and ATO is the only drug used in clinical that targets mitochondria. By combining the effects of SRF and ATO, ATO/SRF@BSA promoted the accumulation of lipid peroxides within mitochondria by inhibiting the glutathione peroxidase 4 (GPX4)-GSH pathway and downregulating the DHODH-coenzyme Q (CoQH2) defense mechanism, triggers a burst of lipid peroxides. Simultaneously, ATO/SRF@BSA suppressed cancer cell self-repair and enhanced cell death by inhibiting the synthesis of adenosine triphosphate (ATP) and pyrimidine nucleotides. Furthermore, the anti-cancer results showed that ATO/SRF@BSA exhibited tumor-specific killing efficacy, significantly improved the tumor hypoxic microenvironment, and lessened the toxic side effects of SRF. This work presents an efficient and easily achievable strategy for TNBC treatment, which may hold promise for clinical applications.

The application of 5E rehabilitation management mode in the nursing of patients with aortic dissection complicated by obstructive sleep apnea.

OBJECTIVE: This study was designed to explore the effect of 5E rehabilitation mode (encouragement, education, exercise, employment, and evaluation) in patients with aortic dissection (AD) complicated by obstructive sleep apnea (OSA). METHODS: Patients with Stanford type B AD (TBAD) complicated by OSA were admitted to Guangdong Provincial People's Hospital from January 2019 to December 2020. They were randomly divided into an experimental group and a control group. After discharge, patients in the control group were given routine nursing and follow-up education, whereas patients in the experimental group were given 5E rehabilitation management mode-based nursing and follow-up education. Upon the nursing intervention, the differences in polysomnography (PSG) parameters, medication adherence, quality of life, blood pressure, and heart rate of patients between the two groups were compared. Logistic regression analysis was performed to evaluate the risk factors for the occurrence of adverse aortic events. RESULTS: A total of 89 patients were enrolled, 49 in the experimental group and 40 in the control group. After the intervention, the control of heart rate, systolic blood pressure, medication adherence, PSG parameters, and quality of life scores in the experimental group were significantly better than those in the control group (P<0.05). The incidence of adverse aortic events including aortic rupture and progressive aortic dilation in the experimental group was significantly lower than that in the control group (P < 0.05). Logistic regression analysis revealed that acute TBAD [odds ratio (OR) = 15.069; 95%confidence interval (CI), 1.738-130.652; P=0.014], history of chronic kidney disease (OR=10.342; 95%CI, 1.056-101.287; P=0.045), and apnea hypopnea index (AHI) ≥ 30 (OR=2.880; 95%CI, 1.081-9.51; P=0.036) were adverse factors affecting adverse aortic events; while 5E rehabilitation management mode (OR=0.063; 95%CI, 0.008-0.513; P=0.010) was a favorable factor for occurrence of adverse aortic events. CONCLUSION: The findings suggest that continuous nursing based on information carrier 5E rehabilitation management significantly enhanced medication adherence, improved patients' overall quality of life, and decreased the incidence of adverse aortic events in patients TBAD patients and OSA.

Prediction of the risk of cytopenia in hospitalized HIV/AIDS patients using machine learning methods based on electronic medical records.

Background: Cytopenia is a frequent complication among HIV-infected patients who require hospitalization. It can have a negative impact on the treatment outcomes for these patients. However, by leveraging machine learning techniques and electronic medical records, a predictive model can be developed to evaluate the risk of cytopenia during hospitalization in HIV patients. Such a model is crucial for designing a more individualized and evidence-based treatment strategy for HIV patients. Method: The present study was conducted on HIV patients who were admitted to Guangxi Chest Hospital between June 2016 and October 2021. We extracted a total of 66 clinical features from the electronic medical records and employed them to train five machine learning prediction models (artificial neural network [ANN], adaptive boosting [AdaBoost], k-nearest neighbour [KNN] and support vector machine [SVM], decision tree [DT]). The models were tested using 20% of the data. The performance of the models was evaluated using indicators such as the area under the receiver operating characteristic curve (AUC). The best predictive models were interpreted using the shapley additive explanation (SHAP). Result: The ANN models have better predictive power. According to the SHAP interpretation of the ANN model, hypoproteinemia and cancer were the most important predictive features of cytopenia in HIV hospitalized patients. Meanwhile, the lower hemoglobin-to-RDW ratio (HGB/RDW), low-density lipoprotein cholesterol (LDL-C) levels, CD4+ T cell counts, and creatinine clearance (Ccr) levels increase the risk of cytopenia in HIV hospitalized patients. Conclusion: The present study constructed a risk prediction model for cytopenia in HIV patients during hospitalization with machine learning and electronic medical record information. The prediction model is important for the rational management of HIV hospitalized patients and the personalized treatment plan setting.

Identification of an antigen-presenting cells/T/NK cells-related gene signature to predict prognosis and CTSL to predict immunotherapeutic response for lung adenocarcinoma: an integrated analysis of bulk and single-cell RNA sequencing.

BACKGROUND: Antigen-presenting cells (APC)/T/NK cells are key immune cells that play crucial roles in fighting against malignancies including lung adenocarcinoma (LUAD). In this study, we aimed to identify an APC/T/NK cells-related gene signature (ATNKGS) and potential immune cell-related genes (IRGs) to realize risk stratification, prognosis, and immunotherapeutic response prediction for LUAD patients. METHODS: Based on the univariate Cox regression and the LASSO Cox regression results of 196 APC/T/NK cells-related genes collected from three pathways in the KEGG database, we determined the final genes and established the ATNKGS-related risk model. The single-cell RNA sequencing data were applied for key IRGs identification and investigate their value in immunotherapeutic response prediction. Several GEO datasets and an external immunotherapy cohort from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were applied for validation. RESULTS: In this study, nine independent public datasets including 1108 patients were enrolled. An ATNKGS containing 16 genes for predicting overall survival of LUAD patients was constructed with robust prognostic capability. The ATNKGS high risk group was related to significantly worse OS outcomes than those in the low-risk group, which were verified in TCGA and four GEO datatsets. A nomogram combining the ATNKGS risk score with clinical TNM stage achieved the optimal prediction performance. The single-cell RNA sequencing analysis revealed CTSL as an IRG of macrophage and monocyte. Moreover, though CTSL was an indicator for poor prognosis of LUAD patients, CTSL high expression group was associated with higher ESTIMATEScore, immune checkpoints expression, and lower TIDE score. Several immunotherapeutic cohorts have confirmed the response-predicting significance of CTSL in patients receiving immune checkpoint inhibitor (ICI) treatment. CONCLUSIONS: Our study provided an insight into the significant role of APC/T/NK cells-related genes in survival risk stratification and CTSL in response prediction of immunotherapy in patients with LUAD.

Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy.

The use of overwhelming reactive oxygen species (ROS) attack has shown great potential for treating aggressive malignancies; however, targeting this process for further applications is greatly hindered by inefficiency and low selectivity. Here, a novel strategy for ROS explosion induced by tumor microenvironment-initiated lipid redox cycling was proposed, which was developed by using soybean phosphatidylcholine (SPC) to encapsulate lactate oxidase (LOX) and sorafenib (SRF) self-assembled nanoparticles (NPs), named LOX/SRF@Lip. SPC is not only the delivery carrier but an unsaturated lipid supplement for ROS explosion. And LOX catalyzes excessive intratumoral lactate to promote the accumulation of large amounts of H2O2. Then, H2O2 reacts with excessive endogenous iron ions to generate amounts of hydroxyl radical for the initiation of SPC peroxidation. Once started, the reaction will proceed via propagation to form new lipid peroxides (LPO), resulting to devastating LPO explosion and widespread oxidative damage in tumor cells. Furthermore, SRF makes contribution to mass LPO accumulation by inhibiting LPO elimination. Compared to normal tissue, tumor tissue has higher levels of lactate and iron ions. Therefore, LOX/SRF@Lip shows low toxicity in normal tissues, but generates efficient inhibition on tumor proliferation and metastasis, enabling excellent and safe tumor-specific therapy. This work offers new ideas on how to magnify anticancer effect of ROS through rational nanosystem design and tumor-specific microenvironment utilization.

Ganoderma lingzhi culture enhance growth performance via improvement of antioxidant activity and gut probiotic proliferation in Sanhuang broilers.

Introduction: The experiment was conducted to evaluate the effects of Ganoderma lingzhi culture (GLC) as a fermented feed on growth performance, serum biochemical profile, meat quality, and intestinal morphology and microbiota in Sanhuang broilers. In addition, the association between gut bacteria and metabolites was investigated via untargeted metabolomic analysis. Methods: A total of 192 Sanhuang broilers (112 days old) with an initial body weight of 1.62 ± 0.19 kg were randomly allocated to four treatments, six replicate pens per treatment with 8 broilers per pen. The four treatments contain a control diet (corn-soybean meal basal diet, CON), a positive control diet (basal diet + 75 mg/kg chlortetracycline, PCON), and the experimental diets supplemented with 1.5 and 3% of GLC, respectively. The trial includes phase 1 (day 1-28) and phase 2 (day 29-56). Results: The results showed that broilers in PCON and GLC-added treatments showed a lower FCR (P < 0.05) in phase 2 and overall period and a higher ADG (P < 0.05) in phase 2. On day 56, the concentrations of serum SOD (P < 0.05), and HDL (P < 0.05) and cecal SCFA contents (P < 0.05) were increased in broilers fed GLC diets. Broilers fed GLC also showed a higher microbiota diversity and an elevated abundance of SCFA-related bacteria in the caecum. The association between intestinal bacteria and metabolites was investigated via correlation analysis. The differential metabolites in the caecum, such as L-beta-aspartyl-L-aspartic acid and nicotinamide riboside, were identified. Conclusion: In summary, dietary GCL supplementation could increase growth performance to some extent. Moreover, GLC might benefit broilers' health by improving serum HDL content, antioxidant status, SCFAs contents, bacterial diversity, and probiotic proliferation in the caecum.

Incidence, survival comparison, and novel prognostic evaluation approaches for stage iii-iv pulmonary large cell neuroendocrine carcinoma and small cell lung cancer.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. METHODS: Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. RESULTS: The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system. CONCLUSIONS: Based on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification.

Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation.

Objective: This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. Methods: Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. Results: In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. Conclusion: Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.

Mental Health of Healthcare Workers during COVID-19 Pandemic in Taiwan: The First Wave Outbreak Occurred 1 Year Later Than in Other Countries.

We probed the psychological influence exerted on traumatic stress endured by healthcare workers (HCWs) and the coping behaviors adopted during the first wave of COVID-19 in Taiwan, which occurred one year later than in other countries. Clinical HCWs from two branches of a hospital network in Taichung, Taiwan, were recruited for this cross-sectional study. The participants were administered a questionnaire on sociodemographic and work-related characteristics, perceived influence exerted by COVID-19, coping behaviors in relation to COVID-19, and Impact of Event Scale-Revised scores. We obtained 769 valid questionnaires. A chi-square test, generalized linear modeling, and multivariate stepwise regression analyses were performed. Although the first wave of COVID-19 occurred one year later in Taiwan than in other countries, the traumatic stress experienced by Taiwanese HCWs was noted to be comparable to that of those in other countries. Factors for increased traumatic stress included caring for more patients with COVID-19, fair or poor self-rated mental health, higher perceived influence of COVID-19, vulnerable household income, and more negative coping behaviors. Positive coping behaviors such as exposure reduction and protection measures decreased traumatic stress. Accordingly, managers should strengthen protective measures, enhance COVID-19-related training, and provide psychological support and counseling for high-risk employees.

Association of immune-related adverse events and efficacy in advanced non-small-cell lung cancer: a systematic review and meta-analysis.

Aim: This study aimed to explore the association of immune-related adverse events (irAEs) with efficacy in advanced non-small-cell lung cancer (NSCLC). Materials & methods: A literature search was conducted under preselected criteria. Primary outcomes were hazard ratio (HR) and 95% CI of irAEs on objective response rate, overall survival (OS) and progression-free survival (PFS). Results: 35 studies covering 8435 patients with advanced NSCLC were included. Patients with irAEs exhibited significantly longer PFS and OS (for PFS, HR: 0.481; 95% CI: 0.370-0.568; p < 0.001 and for OS, HR: 0.470; 95% CI: 0.410-0.539; p < 0.001), and also showed significantly higher objective response rate compared with those without irAEs (pooled OR: 0.023 [95% CI: 0.009-0.590]). Conclusion: This meta-analysis showed that irAEs were associated with efficacy for advanced NSCLC.

Immune-related adverse events (irAEs) are a series of adverse events that occur during the application of immune checkpoint inhibitors. The correlation between irAEs and ICI efficacy is controversial. In this meta-analysis, we analyzed the association of irAEs with the efficacy of immune checkpoint inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). A total of 35 studies covering 8435 patients with NSCLC at advanced stage were included. Pooled analysis demonstrated that patients with irAEs got a significantly higher objective response rate than those without irAEs. Besides this, patients with irAEs had a more favorable survival outcome than those without. This study indicated that the occurrence of irAEs was associated with better survival outcome and higher tumor efficacy for patients with advanced NSCLC.

Effect of anodization on friction behavior of ß­titanium orthodontic archwires.

PURPOSE: To evaluate the effects of anodization on the friction behavior of beta-titanium (ß-Ti) orthodontic archwires in conventional or self-ligating brackets in vitro. METHODS: ß­Ti archwires (0.018â€¯× 0.025 inch) pre- and postanodization were tested in combination with 0.022-inch stainless steel conventional and self-ligating brackets. The surface composition and oxide thickness of the ß­Ti archwires pre- and postanodization were measured using Auger electron spectroscopy (AES) and transmission electron microscopy (TEM). Detailed surface topography and roughness were assessed using atomic force microscopy (AFM). Surface topographies of the ß­Ti archwires pre- and postanodization were examined using scanning electron microscopy (SEM). Friction was measured using a universal testing machine; the data were statistically analyzed. RESULTS: Postanodization, the identified titanium oxide layer on the surface of the ß­Ti archwires increased in thickness from 10 to 100 nm; at the same time, the values for surface roughness were significantly reduced by half (p < 0.001). The archwire surfaces post anodization were harder and had fewer scratches after the friction test. Anodization significantly reduced 23.77% of the static (p < 0.01) and 25.61% of the kinetic (p < 0.001) friction of the ß­Ti archwires in conventional brackets, while it significantly reduced 85.71% of the static and 84.38% of the kinetic friction (p < 0.01) in self-ligating brackets. CONCLUSION: Anodization reduced the ß­Ti archwire friction, which was particularly more effective in combination with self-ligating brackets. The friction reduction via anodization could be attributed to the increased thickness, surface hardness, and decreased surface roughness of the titanium oxide layer.

DLX2 Is a Potential Immune-Related Prognostic Indicator Associated with Remodeling of Tumor Microenvironment in Lung Squamous Cell Carcinoma: An Integrated Bioinformatical Analysis.

Background: It is still an unmet clinical need to identify potent biomarkers for immunotherapy on patients with lung squamous cell carcinoma (LUSC). Methods: In this study, we explored the differentially expressed genes (DEGs) that were simultaneously correlated with four pathways (i.e. CD8+ αßT cell proliferation/differentiation/activation pathways and ferroptosis pathway) and possibly related to the remodeling of tumor microenvironment via the TCGA-LUSC dataset. Besides, four GEO datasets (GSE157009, GSE157010, GSE19188, and GSE126045) and IMvigor210 dataset were utilized for confirmation and validation. Results: The co-downregulated DEG DLX2 was selected for further analysis. Function enrichment analysis revealed that low-expression of DLX2 was closely related to various immune-related pathways like T/B/NK cell mediated immunity, interferon gamma/alpha response, and various autoimmune disease. DLX2-downregulated group was enriched in more immune-activating cells and lower tumor immune dysfunction and exclusion (TIDE) score. Via the Cancer Immunome Atlas (TCIA) database, lower expression of DLX2 was also found to be associated with better IPS score of PD-1/PD-L1 blockade (p < 0.001) as well as CTLA-4 combined with PD-1/PD-L1 blockade (p < 0.001). Furthermore, patients in DLX2-low group were found to have significant longer median OS than those in DLX2-high group in IMvigor210 dataset (10.8 vs 7.4 months; hazard ratio [HR]=0.74, 95% confidence interval [95%CI] 0.57-0.96; p = 0.024). Conclusions: Our study on an integrated bioinformatical analysis implied that DLX2 could be served as a promising indicator for remodeling tumor microenvironment status and predicting ICI response of patients with LUSC.

The exploration of three different treatment models of osimertinib plus antiangiogenic agents in non-small cell lung cancer: A real-world study.

BACKGROUND: Real-world application of osimertinib with antiangiogenic agents in non-small cell lung cancer (NSCLC) is common, but the efficacy data are rarely reported. METHODS: To obtain an objective efficacy report of different real-world treatment models of osimertinib and antiangiogenic agents. RESULTS: A total of 54 patients with NSCLC were enrolled into the study. Twelve (22.2%) who received a combination of antiangiogenic agents, when there was a trend of osimertinib resistance but did not reach imageology progressive disease (PD), were assigned to Group A, with a median overall survival (OS) and progression-free survival (PFS) of 48.0 (95% CI, not reached) and 21.0 (95% CI: 16.7-25.3) months, respectively. Thirty (55.6%) who received a combination of antiangiogenic agents when there was imageology PD during treatment with osimertinib were assigned to Group B, with a median OS and PFS of 31.8 (95% CI: 26.6-37.1) and 9.2 (95% CI: 5.9-12.6) months, respectively. Twelve (22.2%) who received a combination of antiangiogenic agents at the initial treatment with osimertinib were assigned to Group C, with a median OS and PFS of 28.5 (95% CI: 15.2-41.8) and 15.3 (95% CI: 7.9-22.7) months, respectively. Patients in Group A achieved a significant prolonged median PFS (p < 0.001) compared with Groups B and C. Absence of epidermal growth factor receptor (EGFR) T790M mutations (p = 0.043; hazard ratio [HR] = 2.124, 95% CI: 1.023-4.413) and no previous antiangiogenic agent application (p = 0.012; HR = 0.362, 95% CI: 0.163-0.863) were the independent prognostic factors of OS. CONCLUSION: The well-timed action to combine antiangiogenic agents was when there was a trend of osimertinib resistance. The absence of EGFR T790M mutations and previous use of antiangiogenic agents were poor prognostic factors.

The prognostic significance of tumor spread through air space in stage I lung adenocarcinoma.

AIM: There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta-analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. METHODS: Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence-free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. RESULTS: A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p < 0.001) and OS (HR = 2.02, p < 0.001). In subgroup analysis on operation mode, the prognostic value of STAS was prominently shown in patients who underwent limited resection (RFS: HR = 3.58, p < 0.001; OS: HR = 3.37, p < 0.001), while for patients who underwent lobectomy, adverse impact of STAS on RFS was observed (HR = 1.60, p = 0.019), but no significant difference was observed on OS (HR = 1.56, p = 0.061). The results fluctuated in different regions while other factors did not alter the independent predictive value of STAS. CONCLUSION: Tumor STAS should be considered as an adverse prognostic indicator for patients with stage I lung ADC, especially for those under limited resection. More intensive medical care for those patients needs to be investigated in further studies.

Prognostic significance of baseline neutrophil-lymphocyte ratio in patients with non-small-cell lung cancer: a pooled analysis of open phase III clinical trial data.

Aim: This study aimed to assess survival and hematological prognostic indicators of patients with non-small-cell lung cancer (NSCLC). Material & methods: Through the Project Data Sphere portal, two phase III clinical trial datasets were downloaded to analyze survival outcomes and related risk factors. Results: The median progression-free survival and overall survival of 756 patients with stage III-IV NSCLC were 6.2 and 14.2 months, respectively. In multivariate Cox analysis, high baseline neutrophil-lymphocyte ratio (NLR; ≥3.8) was associated with worse progression-free survival (hazard ratio: 1.37; p = 0.0004) and overall survival (hazard ratio: 1.65; p < 0.0001). In addition, it exerted an unfavorable impact on survival across multiple subgroups. Conclusions: NLR, a powerful inflammatory and immunologic indicator, is an independent prognostic indicator in patients with advanced NSCLC.

Effects of a new fermented soya bean meal on growth performance, serum biochemistry profile, intestinal immune status and digestive enzyme activities in piglets.

BACKGROUND: Fermented soya bean meal (FSBM) is believed to have improved nutritional qualities compared with soya bean meal (SBM) and is also cheaper than soya protein concentration (SPC) and fish meal (FM). Therefore, the present study was conducted to compare the effects of FSBM replacing SBM, SPC and FM in diets on growth performance, serum biochemistry profile, short-chain fatty acid concentrations in digesta, intestinal mucosal enzyme activities, intestinal proinflammatory cytokine concentrations and morphology in weaned piglets. One hundred and twenty 28-day-old piglets (Duroc × Landrace × Yorkshire, body weight: 6.73 ± 1.14 kg) were randomly allocated to four treatment diets (six replicate pens with five piglets per pen) containing SBM, SPC, FM or FSBM as the protein source, respectively. RESULTS: Dietary FSBM supplementation improved average daily gain (p < 0.05), gain to feed ratio (p < 0.05), and digestibility of dry matter, gross energy, crude protein and organic matter (p < 0.05) in pigs compared with those fed SBM during 0-14 days and reduced diarrhoea rate (p < 0.05) compared with those fed SBM and FM during 0-14 days. Moreover, pigs fed FBSM had greater IgA and IgM contents and antioxidase activities than those provided SBM and SPC on day 14. In addition, the butyrate concentration in the cecum of pigs fed FSBM was greater than those fed the other diets (p < 0.05), and the trypsin activity in duodenum and jejunum of pigs provided FSBM was greater than those fed SBM (p < 0.05). Moreover, higher villus height (p < 0.05) and villus height to crypt depth ratio (p < 0.05) and lower crypt depth (p < 0.05) in the duodenum of pigs fed FSBM were observed, and pigs fed FSBM had a lower (p < 0.05) TNF-α concentration in jejunum compared with those fed SBM. CONCLUSIONS: In conclusion, dietary FSBM supplementation to replace SBM, SPC and FM could improve piglets' growth performance, intestinal health and immune function.

Nomogram Based on Breast MRI and Clinicopathologic Features for Predicting Axillary Lymph Node Metastasis in Patients with Early-Stage Invasive Breast Cancer: A Retrospective Study.

INTRODUCTION: To establish a nomogram for predicting axillary lymph node (ALN) involvement in patients with early-stage invasive breast cancer (BC) based on magnetic resonance imaging (MRI) features and clinicopathological characteristics. MATERIALS AND METHODS: Patients with confirmed early-stage invasive BC between 03/2016 and 05/2017 were retrospectively reviewed at the National Cancer Center/Cancer Hospital. Risk factors for ALN metastasis (ALNM) were identified by univariable and multivariable logistic regression analysis. The independent risk factors were used to create a nomogram. RESULTS: This study included 214 early-stage invasive BC patients, including 57 (26.6%) with positive ALNs. Tumor location (OR = 4.019, 95% CI: 1.304 -12.383, P = .015), tumor size (OR = 3.702, 95%CI: 1.517 -9.034, P = .004), multifocality (OR = 3.534, 95%CI: 1.249 -9.995, P = .017), MR-reported suspicious ALN (OR = 9.829, 95%CI: 4.132 -23.384, P <0.001), apparent diffusion coefficient (ADC) value (OR = 0.367, 95%CI: 0.158 -0.852, P = .020), and lymphovascular invasion (LVI) (OR = 3.530, 95%CI: 1.483 -8.400, P = .004) were identified as independent risk factors associated with ALNM. A nomogram was created for predicting the probability of ALNM by using these risk factors. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual ALNM rate. The area under the curve was 0.88 (95% CI: 0.83 -0.93). The nomogram had a bootstrapped-concordance index of 0.88 and was well-calibrated. CONCLUSION: The nomogram based on MRI and clinicopathologic features might be a useful tool for predicting ALNM in early-stage invasive BC and could help clinical decision-making.

Analysis on methylation and expression of PSMB8 and its correlation with immunity and immunotherapy in lung adenocarcinoma.

Aim: To find biomarkers for immunity and immunotherapy in lung adenocarcinoma (LUAD) through multiomics analysis. Materials & methods: The multiomics data of patients with LUAD were downloaded from the TCGA and GEO databases. CIBERSORT, quanTIseq, ESTIMATEScore, k-means clustering, gene set enrichment analysis, gene set variation analysis, immunophenoscore and logistic regression were used in this study. Results: PSMB8 HypoMet-HighExp group patients have more active immune-related pathways, more antitumor immune cells, less protumor immune cells, higher immunophenoscore and longer progression-free survival of immune checkpoint inhibitor therapy than HyperMet-LowExp group. In multivariate analysis, PSMB8 showed an independent value. Conclusion: The combination of DNA methylation and mRNA expression of PSMB8 could independently distinguish types of tumor immune microenvironment and predict programmed cell death protein 1/programmed cell death-ligand 1 inhibitors' effects in patients with LUAD.

Our research provides a new and robust method to select biomarkers based on the tumor immune microenvironment. Our research finds that a new epigenomic and transcriptomic biomarker could independently distinguish the types of tumor immune microenvironment and predict immunotherapy effects in patients with lung adenocarcinoma.