Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot.

OBJECTIVE: Continuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. METHODS: Clinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. RESULTS: The joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). CONCLUSION: The joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.

Dietary patterns and life-styles of patients with gastrointestinal involvement of systemic lupus erythematosus: Questionnaire survey from a tertiary center of China.

OBJECTIVE: To investigate the dietary patterns and lifestyles of patients with lupus gastrointestinal (GI) involvement and to reveal the possible role of organ-specific involvement of systemic lupus erythematosus (SLE) on daily diet. METHODS: Patients with SLE complicated with gastrointestinal involvement (SLE-GI) admitted to Peking Union Medical College Hospital (PUMCH) from January 2010 to September 2021 were enrolled. Age- and sex-matched SLE patients with lupus nephritis (SLE-LN) but free of other internal organs involvement who were admitted during the same period were enrolled as disease controls at the ratio of 1:1. In addition, a group of age- and sex-matched healthy people were also included as healthy controls (HCs). Questionnaires were distributed to these patients and HC to collect their dietary patterns and lifestyle information. Clinical features, dietary and lifestyle habits were compared between the two groups of patients and HC. RESULTS: The questionnaire survey showed that compared with HC, the SLE-GI group had higher proportions of vegetarians (p = 0.014) and a lower proportion of omnivores (p = 0.058). A higher percentage of SLE-GI patients reported a traditional Chinese medicine (p = 0.018) taken history and surgical history (p = 0.014). They also less likely to take fried/pickled food (p = 0.042) and dietary supplements (p = 0.024) than HC. Higher percentages of SLE-GI patients and SLE-LN patients preferred self-catering (87.5% and 94.3%) over take-out food than HC (70.8%) (p = 0.127 and p = 0.016). No significant difference on drinking preference among the three groups, but it seemed more SLE-GI patients consumed yogurt than HC (p = 0.097). The SLE-LN patients were also found to have lower frequencies of staying up late (p = 0.005). The SLE-GI group also presented higher positivity rates for anti-SSA (69.6% vs. 45.7%, p = 0.020) and anti-SSB antibodies (32.6% vs. 10.9%, p = 0.011) but lower positivity rates for anti-dsDNA antibodies (30.4% vs. 82.6%, p < 0.001) compared with the SLE-LN group. CONCLUSION: The dietary patterns, life-styles and autoantibody spectrum of SLE-GI patients differed greatly from those of SLE-LN patients and healthy people. These factors may reflect the influence of disease and organ involvement modes on patients' daily life and may contribute partly to the systemic involvement in SLE.

Financial market sentiment and stock return during the COVID-19 pandemic.

Using 1,287,932 pieces of textual data from news media, we measure the financial market sentiment worldwide. We conduct the first international study of the effect of the financial market sentiment on stock return during the COVID-19 pandemic. Results show that the intensification of the epidemic adversely affects the stock market, but the increasing financial market sentiment increases the stock market return, even during the worst of the pandemic. Our results remain robust using alternative proxies. Additional analysis suggests that negative sentiment has a more significant impact on stock market returns than positive sentiment. Taken together, our findings confirm that negative financial market sentiment amplifies the impact of the crisis on the stock market, and positive financial market sentiment can help mitigate the losses caused by the shock.

Concomitant genetic alterations are associated with plasma D-dimer level in patients with non-small-cell lung cancer.

Objective: D-dimer is correlated to the poor prognosis of non-small-cell lung cancer. The study aimed to investigate the association between plasma D-dimer and concomitant mutations in non-small-cell lung cancer. Methods: A total of 517 non-small-cell lung cancer patients were recruited and tested for ALK, BRAF, EGFR, HER2/ERBB2, KRAS, MET, PIK3CA, RET and ROS1 mutation by next-generation sequencing. Multiple gene mutation information, clinical baseline data and laboratory test data were analyzed statistically. Results: All patients were divided into three groups: wild-type group, single-gene mutation group and concomitant mutation group. The analysis of D-dimer, uric acid, gender, family history, smoking history, histology and distant metastasis all showed significant differences in the three groups (p < 0.05). D-dimer was considered as a risk factor for concomitant mutations according to the unordered multiple logistic regression analysis. The receiver operating characteristic curve analysis indicated that D-dimer had an important predictive value for the occurrence of concomitant mutations (area under the curve [AUC]: 0.94; sensitivity: 88.71%; specificity: 86.46). There was significantly shorter median progression-free survival in the concomitant mutation group compared with the single mutation group (7.70 months vs 14.00 months; p = 0.0133). Conclusion: Plasma D-dimer is significantly associated with concomitant mutations and may be regarded as a potent predictor of concomitant mutations for non-small-cell lung cancer patients.

Plain language summary Non-small-cell lung cancer (NSCLC) is a common type of lung cancer. Gene mutation is an important cause of NSCLC. The authors are eager to predict the occurrence of gene mutations through some non-specific indicators. These non-specific indicators need to meet the conditions of simple acquisition and low detection cost. In this study, patients are divided into wild-type, single-gene mutation and concomitant mutation groups based on next-generation sequencing results. The authors have observed that the levels of D-dimer are significantly increased in some NSCLC patients. And D-dimer is considered to be a risk factor for concomitant mutations and had important predictive value for concomitant mutations. This study provides a new predictive and prognostic indicator (D-dimer) for patients with concomitant mutations. D-dimer is a new method for predicting concomitant mutations and guides further treatment in NSCLC.

The efficacy of Raman spectroscopy in lung cancer diagnosis: the first diagnostic meta-analysis.

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion.

Sarcoidosis Stage II: a Case Report and Review of the Literature.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown origin characterized by non-caseous necrotizing epithelial cell granuloma that affects the lung and lymphatic system. Sarcoidosis mainly occurs in young and middle-aged people, usually manifested as bilateral hilar lymph node enlargement, lung infiltration, and eye and skin lesions. Sarcoidosis has a high natural remission rate, but patients with progressive imaging or pulmonary function accompanied by significant clinical symptoms or extrapulmonary lesions need to be treated. METHODS: The sarcoidosis patient had received a 3-month methylprednisolone treatment which significantly improved clinical manifestations including cough and sputum, and extrapulmonary presentation, such as skin nodules and enlargement of parotid glands. RESULTS: A 52-year-old female reporting repeated cough and sputum, with scattered skin rashes and nodules on the extremities, accompanied by nasal congestion, enlargement of abdominal and retroperitoneal lymph nodes and parotid glands was studied. Computed tomography (CT) showed miliary nodules diffusely distributed in both lungs, multiple enlarged lymph nodes in mediastinum, bilateral enlarged hilar lymph nodes, and right pleural effusion. Bronchoscopy with lung biopsy showed granuloma formation, special staining including acid resistance was negative, but signet ring cell carcinoma and tuberculosis cannot be excluded. Biopsy of a skin nodule also showed granulomatosis. PET-CT reported all considered as inflammatory lesions, with a high possibility of tuberculosis. Based on all the information, we confirmed the diagnosis of sarcoidosis stage II. She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications. CONCLUSIONS: Clinical manifestations of this patient are unspecific. Based on the pathological finding, clinical and radiological manifestation, and evidence of no alternative diseases, sarcoidosis stage II is diagnosed. Treatment with a steroid was of benefit in this sarcoidosis patient.

The Feasibility and Effectiveness of Wearable Sensor Technology in the Management of Elderly Diabetics with Foot Ulcer Remission: A Proof-Of-Concept Pilot Study with Six Cases.

AIMS: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication. METHODS: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times. RESULTS: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased. CONCLUSIONS: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.

Sorption properties of cadmium on microplastics: The common practice experiment and A two-dimensional correlation spectroscopic study.

Microplastics (MPs) that have accumulated in the environment are emerging as contaminating pollutants due to their interactions with metal ions. MPs change the migration and transformation of metal ions in the environment and afterward impact their environmental presence. Therefore, it is necessary to evaluate the interaction characteristics and mechanisms between Cd2+and MPs for assessing the ecological impacts of MPs. The traditional sequencing batch equilibrium test demonstrated that the sorption of Cd2+ onto MPs was related to the type of MPs present, the pH value of the solution, the ionic strength of the participants and the presence of humic acid. The sorption dynamics and isotherm experiment illustrated that the interactions were controlled by surface sorption and distribution effects. The specific surface area and surface charge were the main factors in managing the sorption process. FTIR spectra and a 2D-COS analysis showed that different functional groups played an important role in the sorption of Cd2+onto MPs. The results from this work afford new insights on how MPs may play an important role in the fate and transport of heavy metals and present a new analysis method for evaluating the environmental behavior of MPs and their role in transporting other contaminants.

High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome.

BACKGROUND/AIMS: Alarin has been reported to be related with increased food intake and body weight. The relationship of circulating Alarin with insulin resistance or metabolic syndrome (MetS), however, is unknown. This study aimed to investigate the physiological role of Alarin and its association with MetS in humans. METHODS: Newly diagnosed MetS patients (n=237) and age-matched healthy subjects (n=192) were recruited for this study. Oral glucose tolerance test, treadmill exercise, lipid infusions and euglycemic-hyperinsulinemic clamp (EHCs) were performed. Circulating Alarin and TNFα levels were measured by ELISA. RESULTS: Circulating Alarin levels were significantly higher in MetS patients compared with healthy subjects (0.46 ± 0.22 vs. 0.41 ± 0.14 µg/L, P < 0.01). In all studied subjects, circulating Alarin levels were positively correlated with WC, blood pressure, FBG, triglyceride, HbA1c, HOMA-IR, AUCglucose, and TNFα (P < 0.05 or P < 0.01). Multivariate logistic regression analyses revealed that circulating Alarin levels were correlated with MetS and insulin resistance. There was no significant change of circulating Alarin levels in the subjects with treadmill exercise for 45 min. In healthy individuals, however, glucose challenge, acute hyperglycemia and lipid infusions resulted in increased circulating Alarin levels, while acute hyperinsulinaemia transiently decreased circulating Alarin levels. CONCLUSION: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.

2D LiDAR SLAM Back-End Optimization with Control Network Constraint for Mobile Mapping.

Simultaneous localization and mapping (SLAM) has been investigated in the field of robotics for two decades, as it is considered to be an effective method for solving the positioning and mapping problem in a single framework. In the SLAM community, the Extended Kalman Filter (EKF) based SLAM and particle filter SLAM are the most mature technologies. After years of development, graph-based SLAM is becoming the most promising technology and a lot of progress has been made recently with respect to accuracy and efficiency. No matter which SLAM method is used, loop closure is a vital part for overcoming the accumulated errors. However, in 2D Light Detection and Ranging (LiDAR) SLAM, on one hand, it is relatively difficult to extract distinctive features in LiDAR scans for loop closure detection, as 2D LiDAR scans encode much less information than images; on the other hand, there is also some special mapping scenery, where no loop closure exists. Thereby, in this paper, instead of loop closure detection, we first propose the method to introduce extra control network constraint (CNC) to the back-end optimization of graph-based SLAM, by aligning the LiDAR scan center with the control vertex of the presurveyed control network to optimize all the poses of scans and submaps. Field tests were carried out in a typical urban Global Navigation Satellite System (GNSS) weak outdoor area. The results prove that the position Root Mean Square (RMS) error of the selected key points is 0.3614 m, evaluated with a reference map produced by Terrestrial Laser Scanner (TLS). Mapping accuracy is significantly improved, compared to the mapping RMS of 1.6462 m without control network constraint. Adding distance constraints of the control network to the back-end optimization is an effective and practical method to solve the drift accumulation of LiDAR front-end scan matching.

Evidence of "new hot spots" from determining the nonlinear optical behavior of materials: mechanistic studies of the vanadium borate crystal, Na3VO2B6O11.

A novel mechanism for the nonlinear optical (NLO) effects of vanadium borate crystals, Na3VO2B6O11 (NVB), with distorted VO4 groups was investigated. A comprehensive analysis of the structure-property relationship was performed by combining the experimental measurements, the electronic structures calculations, the SHG-weighted electron density and the real-space atom-contribution analysis to yield the linear and nonlinear optical properties. The contribution of a (VO4)(3-) anionic group to the second harmonic generation (SHG) response was more pronounced than that of the (BO3)(3-) anionic group, which plays a virtual role in the SHG effects in NVB. The anionic (BO3)(3-) groups make dominant contributions to the birefringence, whereas the contribution of the V(5+) cations to these linear optical effects is negligible.

Invasive pulmonary aspergillosis accompanied by soft tissue lesions during treatment of a patient with hyperthyroidism: a case report.

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose because it requires histopathology and tissue culture, as well as due to its rapid progression. Invasive pulmonary aspergillosis is the primary cause of pulmonary mycosis in China, which can occur in patients with neutrophil deficiency, leukaemia or lymphoma, malignant tumours, or chronic obstructive pulmonary disease with long-term corticosteroid use or bacterial exacerbations. Such fungal infections can lead to disseminated disease and death within weeks, and the mortality rate for untreated invasive aspergillosis is high. Therefore, increased awareness of invasive aspergillosis in non-traditional hosts is warranted due to the high mortality rate experienced by patients with this disease. Invasive pulmonary aspergillosis has become a principal cause of life-threatening infections in immunocompromised patients. Invasive aspergillosis frequently involves the lung parenchyma and is infrequently accompanied by soft tissue lesions. We present an unusual case of a patient with agranulocytosis that was caused by methimazole that was given to control his hyperthyroidism, and IPA that was accompanied by unusual maxillofacial soft tissue swelling that required treatment with voriconazole. Upon follow-up 11 months later, a chest computed tomography scan (CT) revealed that most lesions had been completely absorbed. Moreover, his maxillofacial ulcers had become encrusted, and the soft tissue swelling had subsided.

Sodium-glucose cotransporter-2 inhibitors and abnormal serum potassium: a real-world, pharmacovigilance study.

BACKGROUND: New trials indicated a potential of sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce hyperkalemia, which might have important clinical implications, but real-world data are limited. Therefore, we examined the effect of SGLT2i on hyper- and hypokalemia occurrence using the FDA adverse event reporting system (FAERS). METHODS: The FAERS database was retrospectively queried from 2004q1 to 2021q3. Disproportionality analyses were performed based on the reporting odds ratio (ROR) and 95% confidence interval (CI). RESULTS: There were 84 601 adverse event reports for SGLT2i and 1 321 186 reports for other glucose-lowering medications. The hyperkalemia reporting incidence was significantly lower with SGLT2i than with other glucose-lowering medications (ROR, 0.83; 95% CI, 0.79-0.86). Reductions in hyperkalemia reports did not change across a series of sensitivity analyses. Compared with that with renin-angiotensin-aldosterone system inhibitors (RAASi) alone (ROR, 4.40; 95% CI, 4.31-4.49), the hyperkalemia reporting incidence was disproportionally lower among individuals using RAASi with SGLT2i (ROR, 3.25; 95% CI, 3.06-3.45). Compared with that with mineralocorticoid receptor antagonists (MRAs) alone, the hyperkalemia reporting incidence was also slightly lower among individuals using MRAs with SGLT-2i. The reporting incidence of hypokalemia was lower with SGLT2i than with other antihyperglycemic agents (ROR, 0.79; 95% CI, 0.75-0.83). CONCLUSION: In a real-world setting, hyperkalemia and hypokalemia were robustly and consistently reported less frequently with SGLT2i than with other diabetes medications. There were disproportionally fewer hyperkalemia reports among those using SGLT-2is with RAASi or MRAs than among those using RAASi or MRAs alone.

Effect of oxygen-containing functional groups on the micromechanical behavior of biodegradable plastics and their formation of microplastics during aging.

Biodegradable plastics (BPs) are more prone to generate harmful microplastics (MPs) in a short time, which have always been ignored. Oxygenated functional group formation is considered to be a key indicator for assessing microplastic formation, while it is difficult to characterize at a very early stage. The micromechanical properties of the aging plastic during the formation of the MPs are highly influenced by the evolution of oxygen-containing functional groups, however, their relationship has rarely been revealed. Herein, we compared changes in the physicochemical properties of BPs and non-degradable plastic bags during aging in artificial seawater, soil, and air. The results showed that the oxidation of plastics in the air was the most significant, with the most prominent oxidation in BPs. The accumulation of carbonyl groups leads to a significant increase in the micromechanical properties and surface brittleness of the plastic, further exacerbating the formation of MPs. It was also verified by the FTIR, 2D-COS, AFM, and Raman spectroscopy analyses. Furthermore, the increased adhesion and roughness caused by oxygen-containing functional groups suggest that the environmental risks of BPs cannot be ignored. Our findings suggest that the testing of micromechanical properties can predicate the formation of the MPs at an early stage.

Variation of Young's modulus suggested the main active sites for four different aging plastics at an early age time.

Precisely determining which bonds are more sensitive when plastic aging occurs is critical to better understand the mechanisms of toxic release and microplastics formation. However, the relationship between chemical bonds with the active aging sites changes and the aging behavior of plastics at an early age is still unclear. Herein, the mechanical behavior of four polymers with different substituents was characterized by the high-resolution AFM. Young's modulus (YM) changes suggested that the cleavage of C-Cl bonds in PVC, C-H bonds in PE and PP, and C-F bonds in PTFE are the main active aging sites for plastic aging. The aging degree of the plastics followed the order of PVC > PP > PE > PTFE. Two aging periods exhibited different YM change behavior, the free radical and cross-linking resulted in a minor increase in YM during the initiation period. Numerous free radicals formed and cross-linking reaction happened, causing a significant increase in YM during the propagation period. Raman spectroscopy verified the formation of microplastics. This research develops promising strategies to quantitatively evaluate the aging degrees using AFM and establish the relationship between chemical bonds and mechanical behavior, which would provide new method to predict plastic pollution in actual environments.

Lactate levels in the brain and blood of schizophrenia patients: A systematic review and meta-analysis.

BACKGROUND: The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism. Many studies have reported changes in the levels of lactate in the brain and serum of schizophrenia patients; however, the results from these studies are not consistent. To overcome this limitation, the goal of the present meta-analysis is to analyze the changes in lactate levels in the brain and blood of schizophrenia patients. METHODS: For this systematic review and meta-analysis, we performed a thorough search of relevant literature in the English language, using the MEDLINE, Cochrane, and Embase databases. RESULTS: In the present meta-analysis, 20 studies were scrutinized, including 13 studies on brain lactate levels, which involved 322 schizophrenia patients and 324 healthy individuals as controls. 7 studies on blood lactate levels, involving 234 schizophrenia patients and 238 healthy individuals, were also included. Brain lactate levels were elevated in schizophrenia patients, both in vivo and in post-mortem studies. Nevertheless, blood lactate levels in schizophrenia patients have revealed no statistically significant difference, as compared with control individuals. CONCLUSIONS: In comparison with healthy individuals, schizophrenia patients had higher lactate levels in the brain, rather than in the blood. These findings suggest independent regulatory mechanisms of lactate levels in the brain and peripheral tissues. Abnormal lactate metabolism in the brain may be an important pathological mechanism in schizophrenia.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy.

OBJECTIVE: Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. METHODS: Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. RESULTS: Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. CONCLUSION: Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.

Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy.

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

Predictive nomogram for bone metastases in lung cancer based on monocyte infiltration.

The presence of bone metastases (BM) in patients with lung cancer is indicative of a worse prognosis. The present study aims to investigate the risk factors associated with BM in patients with lung cancer. Patients with lung cancer admitted to the First Affiliated Hospital of Anhui Medical University between June 2019 and September 2021 were enrolled in this study. A nomogram was constructed based on the outcomes derived from univariate and multivariate analyses. Concordance index, calibration plots, receiver operating characteristic curves, and decision curve analysis were used to evaluate the nomogram. To substantiate the influence of monocytes on lung cancer BM, various assays, including cell co-culture, Transwell, wound-healing assays, and immunohistochemistry and immunofluorescence staining, were conducted. Statistical analyses were performed using SPSS 22.0 software and GraphPad Prism 7.0. A total of 462 eligible patients were enrolled, comprising 220 with BM and 242 without. Multivariate analysis revealed that histological type, medical history, monocyte percentage, and LDH (Lactate Dehydrogenase) and ALP (Alkaline Phosphatase) levels were independent risk factors for BM in lung cancer. Transwell and wound-healing assays indicated that co-culture with monocytes significantly enhanced the migration and invasion capabilities of A549 cells in vitro. Immunohistochemistry and immunofluorescence analyses demonstrated a noteworthy increase in monocyte infiltration in the primary lesions of patients with lung cancer with BM. In conclusion, this study successfully constructed and validated a precise, straightforward, and cost-effective prognostic nomogram for patients with lung cancer with BM.

IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11.

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.