The clinical value of KL-6 for predicting the occurrence and severity of connective tissue disease-associated interstitial lung disease is not affected by CTD type or treatment.

Objective: The aim of this study was to explore the potential values of Krebs von den Lungen-6 (KL-6), neutrophil to lymphocyte ratio (NLR), systemic immune inflammation (SII), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and red blood cell distribution width (RDW) in the diagnosis and evaluation of the severity of connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: A total of 140 connective tissue disease (CTD) patients and 85 CTD-ILD patients were recruited for this study at Shanxi Provincial People's Hospital from May 2022 to May 2023. Patients were divided into subgroups based on medication history and CTD subtypes to compare and analyze the clinical data and laboratory parameters of CTD-ILD patients and CTD patients. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of KL-6, NLR, SII, PLR, MLR, and RDW in identifying CTD-ILD patients from CTD patients. A Spearman correlation analysis was conducted to elucidate the correlations between these markers and the lung function parameters of forced vital capacity (FVC, %), forced expired volume in one second (FEV1, %), and diffusing capacity of carbon monoxide (DLCO, %). Finally, binary logistic regression analysis was applied to discern the independent risk factors for CTD-ILD. Results: NLR, SII, MLR, RDW, and KL-6 displayed significant statistical differences in the experimental groups. In both untreated and treated subgroups, KL-6 displayed higher values for CTD-ILD than CTD among all CTD subtypes. In untreated subgroups, there were significant differences in MLR levels between rheumatoid arthritis (RA) and RA-ILD patients and in NLR levels between Sjögren syndrome (SjS) and SjS-ILD patients. There were also significant differences in RDW-SD between the "other CTD" and "other CTD-ILD" groups. In treated subgroups, there were significant differences in both RDW-SD and RDW-CV between RA and RA-ILD patients and in NLR, SII, MLR, PLR, and RDW-SD between "other CTD" and "other CTD-ILD" groups. ROC revealed that KL-6 emerged as the most effective predictor for CTD-ILD in both treated and untreated groups. The multivariate logistic regression analysis results showed that both KL-6 and age were independent risk factors for CTD-ILD. NLR, SII, and PLR were negatively correlated with DLCO (%) in the untreated CTD-ILD group, and KL-6 was negatively correlated with various lung function parameters in both treated and untreated CTD-ILD groups. Conclusion: KL-6 emerged as the most promising biomarker for diagnosing CTD-ILD and assessing its severity. The diagnostic value of KL-6 was unaffected by medication interference and surpassed the value of other parameters, such as NLR, SII, MLR, and RDW. The diagnostic value of RDW-SD was higher than that of RDW-CV in CTD-ILD patients. NLR, SII, MLR, and PLR have potential value in diagnosing the different types of CTD-ILD.

A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study.

Background: Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method: This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results: Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion: Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Cation-Intercalated Lamellar MoS2 Adsorbent Enables Highly Selective Capture of Cesium.

Highly selective capture of cesium (Cs+) from complex aqueous solutions has become increasingly important owing to its (133Cs) indispensable role in some cutting-edge technologies and the environmental mobility of radioactive nuclide (137Cs) from nuclear wastewater. Herein, we report the development of cation-intercalated lamellar MoS2 as an effective Cs+ adsorbent with the advantages of facile synthesis and highly tunable layer spacing. Two types of cations, including Na+ and NH4+, were employed for the intercalations between adjacent layers of MoS2. The results demonstrated that the adsorption capacity of the NH4+-intercalated material (M-NH4+, 134 mg/g) for Cs+ clearly outperformed the others due to higher loading percentages of cations and larger layer spacing. The cesium partition coefficients for M-NH4+ in the presence of 100-fold competing ions all exceed 1 × 103 mL/g. A simulated complex aqueous solution containing 15.37 mg/L Cs+ and highly excess of competing ions Li+, Na+, K+, Mg2+, and Ca2+ (20-306 times higher) was introduced to prove the practical application potential using our best-performing M-NH4+, showing a good to excellent partition ability of Cs+ among other cations, especially for Cs/K and Cs/Na with separation factors of 58 and 212, respectively. The adsorption and selectivity mechanisms were clearly elucidated using various advanced techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. These results revealed that the good selectivity for Cs+ can be ascribed to the differences in Lewis acidities, hydration energy, cation sizes, and in particular, the divergence of coordination modes which was successfully achieved after tuning the layer distance via the cation intercalation strategy. In addition, the material has fast kinetics (<30 min), wide range of pH tolerance (4-10), and good reusability. Overall, our studies point out that the tunable lamellar MoS2-based materials are promising adsorbents for Cs+ capture and separation.

Regulating the Spin State of Metal and Metal Carbide Heterojunctions for Efficient Oxygen Evolution.

Developing high-performance electrocatalysts for oxygen evolution reaction (OER) is of importance for improving the overall efficiency of water splitting. Herein, the CoFe/(CoxFe1-x)3Mo3C heterojunction is purposely designed as an OER catalyst, which displays a low overpotential of 293 mV for affording a current density of 10 mA cm-2 and a small Tafel slope of 48 mV/dec. Various characterization results demonstrate that the significant work-function difference between CoFe and (CoxFe1-x)3Mo3C can induce interfacial charge redistribution, which results in the formation of Co and Fe sites with a high-spin state, thus stimulating the surface phase reconstruction of CoFe/(CoxFe1-x)3Mo3C to corresponding active oxyhydroxide. Meanwhile, the electrochemical leaching of Mo ions from the initial structure can contribute to the formation of defective sites, further benefiting OH- adsorption and surface oxidation. Moreover, the remaining CoFe can accelerate electron migration during the electrocatalytic process. This study presents new insights into constructing efficient OER electrocatalysts with an optimized spin-state configuration via interfacial engineering.

Current status and future perspectives of immune checkpoint inhibitors in extensive-stage small cell lung cancer.

Small-cell lung cancer (SCLC) is a type of neuroendocrine neoplasms with high aggressiveness and poor prognosis. Chemotherapy has been the standard first-line therapy for SCLC over the past several decades. In recent years, results of randomized phase III CASPIAN and IMpower-133 trials indicated that the combination of immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy improved the overall survival (OS) of patients with extensive stage small-cell lung cancer (ES-SCLC), which has transformed the treatment model for ES-SCLC. ICIs combined with chemotherapy has become the new first-line standard treatment of ES-SCLC with the latest research results from CASPIAN and ASTRUM-005 studies. This review summarizes the recent progress of ICIs in the treatment of ES-SCLC and expounds the mode and efficacy of immunotherapy for ES-SCLC. Future research focused on exploring basic SCLC biology and identifying novel predictive biomarkers in response to ICIs in ES-SCLC is essential. Double-ICIs treatment strategies, bispecific antibodies, and ICIs combined with other therapies, such as chemotherapy, radiotherapy, and targeted therapy, represent a new modality and show great promise for the treatment of ES-SCLC, which should achieve greater therapeutic effects through multiple synergistic mechanisms.

Current status and future perspectives on immunotherapy in neoadjuvant therapy of resectable non-small cell lung cancer.

Resectable non-small cell lung cancer (NSCLC) is defined as stage I-II, and some locally advanced (stage III) tumor. Despite the associated relatively high recurrence rates after surgery, surgical treatment remains the standard treatment for patients with early-stage NSCLC. At present, neoadjuvant therapy is becoming an increasingly popular therapeutic strategy for resectable NSCLC. However, studies have reported that neoadjuvant chemotherapy only slightly improves recurrence rates, making it inadequate for extending patient survival. The significant survival benefits of immunotherapy in advanced NSCLC have greatly stimulated researchers' interests in applying immune checkpoint inhibitors (ICIs) for treating early-stage resectable NSCLC. A few recent phase II radomized clinical trials suggested that ICIs yield better major pathologic response (MPR) rates than neoadjuvant chemotherapy alone, demonstrating their potential as alternatives to the existing fixed therapy pattern for early-stage NSCLC. Most initial studies regarding neoadjuvant immunotherapy selected MPR and pathologic complete response (pCR) as primary or secondary endpoints, leading to a significant reduction in the time and cost of research and development compared with the use of overall survival time and median survival time as endpoints. Meanwhile, to confirm these benefits, more phase III clinical trials are being conducted, and there is a growing demand for research on related problems, including the screening of population, formulation of treatment strategies, duration and course of immunotherapy, influence of neoadjuvant immunotherapy on the safety of surgery, standardization of treatment effect evaluation and pathologic evaluation, and ways to effectively identify pseudoprogression and avoid resultant misjudgment in surgery and adjuvant therapy.

Cardiovascular risk profile and clinical characteristics of diabetic patients: a cross-sectional study in China.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in adults with type 2 diabetes (T2D). The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) guidelines on diabetes, pre-diabetes, and CV diseases. METHODS: A total of 25,411 patients with T2D, who participated in the study of China Cardiometabolic Registries 3B study, were included in our analysis. We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines. RESULTS: Based on the 2019 ESC/EASD guidelines, 16,663 (65.6%), 1895 (7.5%), and 152 (0.6%) of patients were included in "very high risk," "high risk," and "moderate risk" categories, respectively. The proportions of patients in each category varied based on age, sex, body mass index, and duration. While 58.7% (9786/16,663) of elderly patients were classified to "very high risk" group, 89.6% (3732/4165) of patients with obesity were divided into "very high risk" group. Almost all patients with a duration of diabetes >10 years had "very high risk" or "high risk." However, 6701 (26.4%) of Chinese T2D patients, who had shorter duration, and one or two risk factors, could not be included in any category (the "unclear risk" category). CONCLUSIONS: In China, most patients with T2D have "very high" or "high" CV risk based on 2019 ESC/EASD guidelines. However, the risk of patients in "unclear risk" group needs to be further classified.

Immunotherapy versus standard chemotherapy for treatment of extensive-stage small-cell lung cancer: a systematic review.

Aim: We conducted a systematic review and network meta-analysis to evaluate the efficacy of immunotherapy versus chemotherapy to treat extensive-stage small-cell lung cancer. Methods: We analyzed several eligible clinical trials using fixed or random-effects models to evaluate relative treatment effects depending on heterogeneity. Results: In the experimental group, immunotherapy showed significant improvement in overall survival (hazard ratio [HR]: 0.82; 95% CI: 0.74-0.89; I2 = 31.4%; p < 0.001) and progression-free survival (HR: 0.77; 95% CI: 0.80-0.83; I2 = 22.7%; p < 0.001). Conclusion: Immunotherapy is likely to significantly improve extensive-stage small-cell lung cancer patients' overall survival and progression-free survival compared with standard chemotherapy. Anti-PD L1 exhibited superior overall survival compared with anti-PD 1 and anti-CTLA4.

Lay abstract In the past decades, therapy of small-cell lung cancer (SCLC) has maintained the status quo in that etoposide, in combination with platinum-based chemotherapy, is still the first-line treatment for SCLC. Despite cancer cells being very sensitive to standard chemotherapy, relapse rates and prognosis are poor, especially in extensive-stage small-cell lung carcinoma (ES-SCLC). It is meaningful that immune checkpoint inhibitors have led to a promising transformation of treatment models for ES-SCLC. We searched the related literature systematically and performed a meta-analysis of several clinical trials to compare chemotherapy's therapeutic efficacy with immunotherapy. We found that immune checkpoint inhibitors achieve great improvement in survival indexes of ES-SCLC patients compared with standard chemotherapy.

Donor-Acceptor Couples of Metal and Metal Oxides with Enriched Ni3+ Active Sites for Oxygen Evolution.

Exploiting precious-metal-free and high-activity oxygen evolution reaction (OER) electrocatalysts has been in great demands toward many energy storage and conversion processes, for example, carbon dioxide reduction, metal-air batteries, and water splitting. In this study, the simple solid-state method is employed for coupling Ni (electron donors) with lower-Fermi-level MoO2 or WOx (electron acceptors) into donor-acceptor ensembles with well-designed interfaces as robust electrocatalysts for OER. The resulting Ni/MoO2 and Ni/WOx electrocatalysts exhibit smaller overpotentials of 287 and 333 mV at 10 mA cm-2 as well as smaller Tafel slopes of 51 and 65 mV/dec, respectively, with respect to the single Ni, MoO2, WOx, and even the benchmark RuO2 in 1 M KOH. Specially, on account of a higher Fermi level of Ni in comparison with MoO2 and WOx, their strong electronic interaction results in directional interfacial electron transfer and increases the hole density over Ni, dramatically enriching the population of high-valence Ni3+ active sites and decreasing the Fermi level of Ni. The existence of Ni3+ can strengthen the chemisorption of OH-, and the downshift of the Ni Fermi level can significantly expedite migration of electrons toward the surface of catalysts during OER, thus synergistically boosting the OER catalytic performance. Furthermore, the inner Ni/MoO2 and Ni/WOx heterostructures and the electrochemically induced surface layers of oxides/hydroxides collectively boost the OER kinetics. This study highlights the importance of designing highly efficient OER electrocatalysts with high-valence active species (Ni3+) and better matched energy levels induced by the work function difference through interfacial engineering.

Analysis of Circulating Microvesicles Levels and Effects of Associated Factors in Elderly Patients With Obstructive Sleep Apnea.

Background: The incidence of obstructive sleep apnea (OSA) in the elderly is high, and the disorder is associated with a variety of chronic diseases. Microvesicles (MVs) are extracellular vesicles secreted by various cells during stimulation or apoptosis that play an important role in the pathogenesis of OSA. However, concentrations of circulating MVs in elderly patients with OSA remain unclear. Methods: Patients aged >60 years old were recruited and underwent polysomnography. Circulating plasma MV concentrations, including annexin V+MVs, endothelial MVs (EMVs), platelet MVs (PMVs), and leukocyte MVs (LMVs) levels, were measured using a flow cytometer with different labeling methods. Potential factors affecting the concentration of circulating MVs in elderly patients with OSA were determined via Spearman's correlation and multiple linear regression analysis. Results: Levels of circulating MVs, including both single- (annexin V+MVs, CD144+EMVs, CD41a+PMVs, and CD45+LMVs) and dual-labeled MVs (annexin V+CD144+EMVs), were elevated in elderly patients with OSA. Circulating MVs were positively correlated with OSA severity (AHI, ODI, and SPO2min). To some extent, obesity affected the MV concentrations in elderly patients with OSA. In addition, age and comorbidities may be associated with MV levels, but the correlations between the MV levels and age or comorbidities were not significant. Conclusion: Concentrations of circulating MVs in elderly patients with OSA are associated with the labeling method used, OSA severity, and obesity. The effects of age and comorbidities on circulating MV levels require further verification using a larger sample size.

Sex differences in the prevalence of obesity in 800,000 Chinese adults with type 2 diabetes.

AIMS: To estimate the sex differences in the prevalence of overweight and obesity aged 20-89 in Chinese patients with type 2 diabetes (T2D). METHODS: 811,264 patients with T2D from six hospital-based, cross-sectional studies, and 46,053 subjects from the general population were included in our analysis. Prevalence of underweight, overweight, obesity were calculated in each sex. RESULTS: In patients with T2D, the standardized prevalence of underweight (BMI <18.5 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and general obesity (BMI ≥28 kg/m2) were 2.2%, 43.2%, and 11.6%, respectively. Similar trend patterns of the prevalence of underweight and overweight were observed in general and T2D population, in males and females with T2D (all P for trend <0.01). In patients with T2D, patients at a younger age and older age were more likely to be underweight. The prevalence of overweight increased first, then stabilized or decreased with age. However, different trend patterns of the prevalence of obesity in males and females were found. In males, the prevalence of obesity decreased first, and then stabilized after 60 years of age. In females, the prevalence of obesity decreased first, then increased after 50 years of age. In the general population, the prevalence of obesity increased with age in females, while, the trend of prevalence of obesity with age in males was not obvious. CONCLUSION: Different trends in the prevalence of obesity with age in different sex were found in Chinese patients with T2D.

Crosstalk between exosomes and autophagy: A review of molecular mechanisms and therapies.

Exosomes are extracellular vesicles that primarily exist in bodily fluids such as blood. Autophagy is an intracellular degradation process, which, along with exosomes, can significantly influence human health and has therefore attracted considerable attention in recent years. Exosomes have been shown to regulate the intracellular autophagic process, which, in turn, affects the circulating exosomes. However, crosstalk between exosomal and autophagic pathways is highly complex, depends primarily on the environment, and varies greatly in different diseases. In addition, studies have demonstrated that exosomes, from specific cell, can mitigate several diseases by regulating autophagy, which can also affect the excessive release of some harmful exosomes. This phenomenon lays a theoretical foundation for the improvement of many diseases. Herein, we review the mechanisms and clinical significance of the association and regulation of exosomes and autophagy, in order to provide a new perspective for the prevention and treatment of associated diseases.

Achieving Effective and Efficient Basal Insulin Optimal Management by Using Mobile Health Application (APP) for Type 2 Diabetes Patients in China.

AIM: To evaluate the effectiveness of the mobile health application (APP) education in basal insulin optimal management program for insulin-naive type 2 diabetes (T2D) patients in China. METHODS: The basal insulin optimal management program was launched in 297 hospitals in China, throughout the six main regions of China. A total of 17,208 insulin-naive patients with T2D who started to use basal insulin were screened. The mobile health APP was downloaded in each recruited patient's mobile phone and the doctor's mobile phone. Then, according to the instructions and education materials in the APP, these patients began their self-management of insulin dosage titrations and contacted their doctors by APP if they need help. RESULTS: Overall, 12,530 patients with T2D were finally included in the analysis. The average age was 51.97±12.76 years, and 58% of them were males. The average body mass index is 24.46±3.83 kg/m2, and the average HbA1c at baseline was 8.33±2.11% with 24% of the subjects reaching the target of HbA1c<7.0% at baseline. After 3 months of treatment and educations through the APP, HbA1c decreased significantly from baseline (-1.02±1.72%), with 59% of the patients reaching HbA1c<7.0%. After 6 months, the glycemic control of HbA1c also decreased from baseline significantly (-1.01±1.67%). Dosage of insulin daily was 0.23±0.09 IU/kg at baseline, and 0.23±0.23 IU/kg after 6 months of treatment. Regarding the profiles of hypoglycemia treatment, 3145 patients received basal insulin in combination with mono oral anti-diabetic drug (OAD), 1204 patients with dual OADs, 208 patients with triple OADs, and 17 patients with quarter OADs. CONCLUSION: Patients could benefit from the basal insulin optimal management program in self-management by using mobile health APP educations. For T2D patients who are going to start insulin treatment, mobile health APP can help them to reach the target of glycemic control with appropriate dosage of insulin.