A double-emission molecularly imprinted ratiometric fluorescent sensor based on carbon quantum dots and fluorescein isothiocyanate for visual detection of p-nitroaniline.

A novel molecularly imprinted ratiometric fluorescent sensor CQDs@MIP/FITC@SiO2 for the detection of p-nitroaniline (p-NA) was constructed through the mixture of CQDs@MIP and FITC@SiO2 in the ratio of 1:1 (VCQDs@MIP:VFITC@SiO2). The polymers of CQDs@MIP and FITC@SiO2 were prepared by sol-gel method and reversed-phase microemulsion method, respectively. CQDs@MIP was used as the auxiliary response signal and FITC@SiO2 was used as the reference enhancement signal. The signal was measured at excitation/emission wavelengths of 365/438, 512 nm. The sensor showed good linearity in the concentration range 0.14-40.00 µM (R2 = 0.998) with a detection limit of 0.042 µM for p-NA. The color change of "blue-cyan-green" could be observed by the naked eye under 365 nm UV light, thus realizing the visual detection of p-NA. The sensor presented comparable results compared with high-performance liquid chromatography (HPLC) method for the detection of p-NA in hair dye paste and aqueous samples with recoveries of 96.8-103.7% and 95.8-104.4%, respectively. It was demonstrated that the constructed sensor possesses the advantages of simplicity, excellent selectivity, superior sensitivity, and outstanding stability.

Accurate measurement techniques and prediction approaches for the in-situ rock stress.

The precise calculation and evaluation of the in-situ rock stress tensor is a crucial factor in addressing the major challenges related to subsurface engineering applications and earth science research. To improve the accuracy of in-situ stress measurement and prediction, an improved overcoring technique involving a measurement circuit, temperature compensation, and calculation method is presented for accurately measuring the in-situ rock stress tensor. Furthermore, an embedded grey BP neural network (GM-BPNN) model is established for predicting in-situ rock stress values. The results indicate that the improved overcoring technique has significantly improved the stress measurement accuracy, and a large number of valuable stress data obtained from many mines have proved the testing performance of this technique. Moreover, the mean relative errors of the prediction results of GM(0, 1) for the three principal stresses all reach 6-30%, and the accuracy of the model fails to meet the requirements. The average relative errors of the prediction results of the BPNN model are all less than 10%, and the model accuracy meets the requirements and has sufficient credibility. Compared with the GM and BPNN models, the embedded GM-BPNN model produces the best results, with mean relative errors of 0.0001-4.8338%. The embedded GM-BPNN model fully utilizes the characteristics of grey theory and BP neural network, which require a small sample size, weaken the randomness of the original data, and gradually approach the accuracy of the model, making it particularly suitable for situations with limited stress data.

Winter harvesting reduces methane emissions and enhances blue carbon potential in coastal phragmites wetlands.

Enhancing the ability of coastal blue carbon to accumulate and store carbon and reduce net greenhouse gas emissions is an essential component of a comprehensive approach for tackling climate change. The annual winter harvesting of Phragmites is common worldwide. However, the effects of harvesting on methane (CH4) emissions and its potential as an effective blue carbon management strategy have rarely been reported. In this study, the effects of winter Phragmites harvesting on the CH4 and carbon dioxide (CO2) fluxes and the underlying mechanisms in coastal Phragmites wetlands were investigated by comparing the eddy covariance flux measurements for three coastal wetlands with different harvesting and tidal flow conditions. The results show that harvesting can greatly reduce the CH4 emissions and the radiative forcing of CH4 and CO2 fluxes in coastal Phragmites wetlands, suggesting that winter Phragmites harvesting has great potential as a nature-based strategy to mitigate global warming. The monthly mean CH4 fluxes were predominantly driven by air temperature, gross primary productivity, and latent heat fluxes, which are related to vegetation phenology. Additionally, variations in the salinity and water levels exerted strong regulation effects on CH4 emissions, highlighting the important role of proper tidal flow restoration and resalinization in enhancing blue carbon sequestration potential. Compared with the natural, tidally unrestricted wetlands, the CH4 fluxes in the impounded wetland were less strongly correlated with hydrometeorological variables, implying the increased difficulties of predicting CH4 variations in impounded ecosystem. This study facilitates the improved understanding of carbon exchange in coastal Phragmites wetlands with harvesting or impoundment, and provides new insights into effective blue carbon management strategies beyond tidal wetland restoration for mitigating the effects of climate change.

A Comparative Study of 2 Techniques to Avoid Bone Cement Loosening and Displacement After Percutaneous Vertebroplasty Treating Unstable Kummell Disease.

Objective: Percutaneous vertebroplasty (PVP) is currently the most common surgical procedure for unstable Kummell disease (KD), but bone cement loosening or displacement often occurs after the operation. We had been using percutaneous pediculoplasty (PPP) or a self-developed bone cement bridging screw system to avoid this severe complication. This study intends to compare the safety, advantages and disadvantages of these 2 novel surgical procedures through a 2-year follow-up evaluation. Methods: In accordance with the inclusion and exclusion criteria, from May 2017 to May 2021, 77 patients with single segmental unstable KD who had received the PVP-PPP combined therapy were included in the PPP group, and 42 patients with the same who had received the PVP-bone cement bridging screw system combined therapy were included in the screw group. All patients received the operation through unilateral approach. The changes in the vertebral body index (VBI), bisegmental Cobb angle, visual analogue scale (VAS) and Oswestry Disability Index (ODI) and the bone cement loosening rate and displacement rate at different follow-up time points were used to evaluate the clinical efficacy. Results: The average operation duration of the PPP group was 85.52±10.78 minutes (range, 70-115 minutes), and its average bone cement injection volume was 4.98±0.67 mL (range, 4-6 mL). The average operation duration of the screw group was 52.07±9.90 minutes (range, 36-65 minutes), and its average bone cement injection volume was 4.43±0.89 mL (range, 2.5-6 mL). Before operation, immediately after operation and at 6 months after operation, there was no significant difference in VBI or bisegmental Cobb angle between the screw group and the PPP group (p>0.05), while at 1-year and 2-year midterm postoperative evaluations, the screw group had higher VBI and bisegmental Cobb angle than the PPP group (p<0.05). Before operation, immediately after operation, at 6 months after operation and at 1 year after operation, there was no significant difference in VAS or ODI score between the screw group and the PPP group (p>0.05), while at 2 years after operation, the screw group still had higher VAS and ODI scores than the PPP group (p<0.05). No bone cement displacement occurred in both groups, but the rate of bone cement loosening was 14.29% in group PPP, and 0 in screw group (p<0.05). Conclusion: This 2-year follow-up study shows that the PVP-bone cement bridging screw system combined therapy had better midterm treatment efficacy than the PVP-PPP combined therapy in patients with unstable KD, and the bone cement bridging screw system is a preferred therapy with better anti cement loosening ability.

Effect of butylphthalide on prevention and treatment of high altitude cerebral edema in rats.

3-n-butylphthalide (NBP) contains one of the main active ingredients of celery seed. It has a series of pharmacological mechanisms, including reconstitution of microcirculation, protection of mitochondrial function, inhibition of oxidative stress, and inhibition of neuronal apoptosis. Based on the complex multi-targeting of NBP pharmacological mechanisms, the clinical applications of NBP are increasing, and more and more clinical studies and animal experiments have focused on NBP. In this study, we used male Sprague Dawley rats as an animal model to elucidate the intervention effect of butylphthalide on high altitude cerebral edema (HACE), and also compared the effect of butylphthalide and rhodiola rosea on HACE. Firstly, we measured the changes of body weight and brain water content and observed the pathological changes of brain tissues. In addition, the contents of inflammatory factors, oxidative stress and brain neurotransmitters were assessed by enzyme-linked immunoassay kits, and finally, the expression of apoptotic proteins in brain tissues was determined by western blotting. The results showed that NBP reduced brain water content, attenuated brain tissue damage, altered inflammatory factors, oxidative stress indicators, and brain neurotransmitter levels, and in addition NBP inhibited the expression of Caspase-related apoptotic proteins. Therefore, NBP has the potential to treat and prevent HACE.

Predictive Value and Immunological Role of the HSPA5 Gene in Cervical Cancer.

Cervical cancer (CC) ranks fourth among women's malignancies worldwide and seriously affects women's health. HSPA5 is a heat shock protein, also known as glucose regulatory protein 78 (GRP78). Upregulation of HSPA5 has been reported to be closely associated with multiple types of tumors. However, the specific role of HSPA5 in cervical cancer has not been discovered. In our study, we explored the prognostic value of HSPA5 in CC. Here, we analyzed the (TCGA) and (UCSC) databases, the analysis of HSPA5 in many tumors types was conducted with the "wilcox. test" method. A False Discovery Rate (FDR) value < 0.05 and Log2 | (fold change, FC) |> 1 were set as the cutoffs. "*", "**", and "***" indicate FDR < 0.05, < 0.01, and < 0.001, respectively, and further used human cervical cancer cells for q-PCR and western blotting detection. q-PCR and western blotting results showed that HSPA5 was highly expressed in cervical cancer cells, while it was expressed at low levels in normal cells (P < 0.05).We also analyzed the immunohistochemical data. immunohistochemical analysis results showed that HSPA5 was highly expressed in human cervical cancer, while it was expressed at low levels in normal tissues (P < 0.05). Analysis in TCGA-UCSC showed that the proportion of G3 in the group with high expression of HSPA5 was relatively high (P < 0.05). Enrichment analysis and survival analysis showed that the increased expression of HSPA5 in cervical cancer was related to the survival of CC and was involved in the regulation of biological behavior and molecular signaling pathways of cervical cancer. The correlation analysis of immune checkpoint and immune infiltration showed that HSPA5 was involved in the regulation of immune process of cervical cancer (P < 0.05). Drug sensitivity correlation analysis showed that HSPA5 was a sensitive target for tumor drugs (P < 0.05). In brief, those results suggest that HSPA5 can act as an oncogene of CC development and can serve as an effective predictive biomarker in cervical cancer.

Comparison and evaluation of overcoring and hydraulic fracturing stress measurements.

The stress measurements determined by both the overcoring (OC) and hydraulic fracturing (HF) methods in the Shuichang iron mine and Sanshandao gold mine were compared and evaluated, respectively. The results indicate that the independent OC and HF data in the two mines reveal the same dominant faulting stress regime. The σH orientations derived from the OC and HF methods in the Shuichang iron mine are dominantly oriented in the N81.1°W-N89.4°W and N77.0°E-N88.0°E, respectively, and the σH orientations yielded from the OC and HF techniques in the Sanshandao gold mine are predominantly in the N30°W-N90°W and N55.5°W-N60.4°W, respectively; hence, the σH orientations obtained by the two different methods in the two mines are comparatively similar. In addition, the shapes of the probability density diagrams using an improved Bayesian regression approach of the three principal stresses measured by the OC and HF methods in the same mine are quite similar, and all the obtained Kolmogorov-Smirnov test p-values are larger than the selected significance level of 0.01, indicating that the stress data interpreted by the two methods approximately follow the same distribution law. Thus, the performance of the two techniques and the reliability of the measured data are satisfactory.

Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury.

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION: In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.

Single and combined toxic effects of nCu and nSiO2 on Dunaliella salina.

There are many studies on the toxic effects of single nanoparticles on microalgae; however, many types of nanoparticles are present in the ocean, and more studies on the combined toxic effects of multiple nanoparticles on microalgae are needed. The single and combined toxic effects of nCu and nSiO2 on Dunaliella salina were investigated through changes in instantaneous fluorescence rate (Ft) and antioxidant parameters during 96-h growth inhibition tests. It was found that the toxic effect of nCu on D. salina was greater than that of nSiO2, and both showed time and were dose-dependent with the greatest growth inhibition at 96 h. A total of 0.5 mg/L nCu somewhat promoted the growth of microalgae, but 4.5 and 5.5 mg/L nCu showed negative growth effects on microalgae. The Ft of D. salina was also inhibited by increasing concentrations of nanoparticles and exposure time. nCu suppressed the synthesis of TP and elevated the MDA content of D. salina, which indicated the lipid peroxidation of algal cells. The activities of SOD and CAT showed a trend of increasing and then decreasing with the increase of nCu concentration, suggesting that the enzyme activity first increased and then decreased. The toxic effect of a high concentration of nCu was reduced after the addition of nSiO2. SEM and EDS images showed that nSiO2 could adsorb nCu in seawater. nSiO2 also adsorbed Cu2+ in the cultures, thus reducing the toxic effect of nCu on D. salina to a certain extent. TEM image was used to observe the morphology of algal cells exposed to nCu.

Preparation of surface molecularly imprinted polymers with Fe3O4/ZIF-8 as carrier for detection of Dimethoate in cabbage.

In this study, molecularly imprinted polymers (MIPs) were prepared for the specific recognition of organophosphorus pesticides and a rapid, efficient and simple method was established for the detection of dimethoate (DIT) in food samples. Fe3O4 magnetic nanoparticles were synthesized by co-precipitation, and Fe3O4/ZIF-8 complexes were prepared by a modified in-situ polymerization method, and then magnetic molecularly imprinted polymers (MMIPs) were prepared and synthetic route was optimized by applying density functional theory (DFT). The morphological characterization showed that the MMIPs were coarse porous spheres with an average particle size of 50 nm. The synthesized materials are highly selective for the organophosphorus pesticide dimethoate with an adsorption capacity of 461.50 mg·g-1 and are effective resistance to matrix effects. A novel method for the determination of DIT in cabbage was developed using the prepared MMIPs in combination with HPLC. The practical results showed that the method can meet the requirements for the determination of DIT in cabbage with recoveries of 85.6-121.1 % and detection limits of 0.033 µg·kg-1.

Molecularly imprinted ratiometric fluorescence sensor for visual detection of 17ß-estradiol in milk: A generalized strategy toward imprinted ratiometric fluorescence construction.

17ß-Estradiol (E2) is the typical endocrine disruptor of steroidal estrogens and is widely used in animal husbandry and dairy processing. In the environment, even lower concentrations of E2 can cause endocrine dysfunction in organisms. Herein, we have developed a novel molecularly imprinted ratiometric fluorescent sensor based on SiO2-coated CdTe quantum dots (CdTe@SiO2) and 7-hydroxycoumarin with a post-imprint mixing strategy. The sensor selectively detected E2 in aqueous environments due to its two fluorescent signals with a self-correction function. The sensor has been successfully used for spiking a wide range of real water and milk samples. The results showed that the sensor exhibited good linearity over the concentration range 0.011-50 µg/L, obtaining satisfactory recoveries of 92.4-110.6% with precisions (RSD) < 2.5%. Moreover, this sensor obtained an ultra-low detection limit of 3.3 ng/L and a higher imprinting factor of 13.66. By using estriol (E3), as a supporting model, it was confirmed that a simple and economical ratiometric fluorescent construction strategy was provided for other hydrophobic substances.

Allelochemicals of Alexandrium tamarense and its algicidal mechanism for Prorocentrum donghaiense and Heterosigma akashiwo.

The effects of culture filtrate of Alexandrium tamarense on Prorocentrum donghaiense and Heterosigma akashiwo were investigated, including determination of algal density, photosynthesis, intracellular enzyme content and activity. The filtrate of A. tamarense had a stronger inhibitory effect on P. donghaiense than H. akashiwo, and the inhibitory effect decreased with higher temperature treatment of the filtrate. Instantaneous fluorescence (Ft) and maximum quantum yield of photosystem II (Fv/Fm) values of both kinds of target algae were reduced as exposed to the filtrate of A. tamarense, which proved that allelopathy could inhibit the normal operation of photosynthetic system. The increase of Malondialdehyde (MDA) content of the two kinds of target algae indicated that the cell membrane was seriously damaged by allelochemicals released by A. tamarense. The different responses of Superoxide Dismutase (SOD) and Catalase (CAT) activity in two kinds of target algae demonstrated the complexity and diversity of allelopathic mechanism. The filtrate of A. tamarense also influenced the metabolic function (ATPases) of P. donghaiense and H. akashiwo, and the influence on P. donghaiense was greater. Liquid-liquid extraction was used to extract and isolate allelochemicals from the filtrate of A. tamarense. It was found that only component I with molecular weight of 424.2573 and 434.2857 could inhibit the growth of P. donghaiense by HPLC-MS.

Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection.

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.

Pyrolysis of exhausted biochar sorbent: Fates of cadmium and generation of products.

Biochar is a promising sorbent for Cd removal from water, while the disposal of the exhausted Cd-enriched biochar remains a challenge. In this study, pyrolysis was employed to treat the exhausted biochar under N2 and CO2 atmospheres at 600-900 °C, and the fate of Cd during pyrolysis and characteristics of high-valued products were determined. The results indicated that higher temperature and CO2 atmosphere favored the volatilization of Cd. Based on the toxicity characteristic leaching procedure (TCLP) results, the pyrolysis treatment under both atmospheres enhanced the stability of Cd, and the leached Cd concentration of regenerated biochar obtained at high temperatures (>800 °C) was lower than 1 mg/L. Compared with the pristine biochar, the regenerated biochar demonstrated higher carbon content and pH, whereas the contents of oxygen and hydrogen declined, and exhibited promising sorption properties (35.79 mg/g). The atmosphere played an important role in modifying biochar properties and syngas composition. The N2 atmosphere facilitated CH4 production, whereas the CO2 atmosphere increased the proportion of CO. These results implied that pyrolysis can be a valuable and environmental-friendly strategy for the treatment and reuse of exhausted biochar sorbent.

The effect of N-methyl-D-aspartate receptor antagonists on the mismatch negativity of event-related potentials and its regulatory factors: A systematic review and meta-analysis.

This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs) in healthy subjects and explores whether NMDAR antagonists have different effects on MMN components under different types of antagonists, drug dosages, and deviant stimuli. We conducted a comprehensive literature search of PubMed, EMBASE, and the Cochrane Library from inception to August 1, 2023 for studies comparing the MMN components between the NMDAR antagonist intervention group and the control group (or baseline). All statistical analyses were performed using Stata version 12.0 software. Sixteen articles were included in the systematic review: 13 articles were included in the meta-analysis of MMN amplitudes, and seven articles were included in the meta-analysis of MMN latencies. The pooled analysis showed that NMDAR antagonists reduced MMN amplitudes [SMD (95% CI) = 0.32 (0.16, 0.47), P < 0.01, I2 = 47.3%, p < 0.01] and prolonged MMN latencies [SMD (95% CI) = 0.31 (0.13, 0.49), P = 0.16, I2 = 28.3%, p < 0.01]. The type of antagonist drug regulates the effect of NMDAR antagonists on MMN amplitudes. Different antagonists, doses of antagonists, and types of deviant stimuli can also have different effects on MMN. These findings indicate a correlation between NMDAR and MMN, which may provide a foundation for the application of ERP-MMN in the early identification of NMDAR encephalitis.

Geometric remodeling of tricuspid valve in pulmonary hypertension and its correlation with pulmonary hypertension severity: a prospectively case-control study using four-dimensional automatic tricuspid valve quantification technology.

Background: Evaluation of the tricuspid valve (TV) is crucial for clinical decision making and post-treatment follow-up in pulmonary hypertension (PH) patients. However, little is known about 4-dimensional (4D) TV geometric remodeling in patients with PH. The aim of this study was to examine the 4D geometry of the TV in PH and its correlation with PH severity. Methods: A total of 74 PH patients with mean pulmonary arterial pressure >25 mmHg and 15 age- and gender-matched healthy individuals were consecutively included from September 2017 to December 2018 in National Center for Cardiovascular Diseases, Fuwai Hospital. All participants underwent 2-dimensional (2D) and 4D transthoracic echocardiography and PH patients underwent right heart catheterization (RHC) within 48 hours of echocardiography. TV geometry was analyzed using a dedicated 4D echocardiography from the right ventricular-focused apical view. Results: Compared with controls, PH patients had significantly larger 4D tricuspid annular (TA) and TV tenting sizes except in the 2-chamber diameter. In high-quality image cases, maximal tenting height (MTH), coaptation point height, tenting volume and 4-chamber diameter had good or moderate correlation with PH severity graded according to RHC mean pulmonary artery pressure (r=0.705, r=0.644, r=0.602, r=0.472, respectively; P<0.001 for all). In multivariable linear regression analysis, PH severity was independently associated with coaptation point height (F=18.070, P<0.001 with an R2=0.647) and MTH (F=25.576, P<0.001 with an R2=0.378). Among all 4D TV parameters, MTH had the highest area under the receiver operating characteristic (ROC) curve (AUC) in high-quality image cases [AUC =0.857, 95% confidence interval (CI): 0.743-0.972; P<0.001], comparable to echocardiographic systolic pulmonary arterial pressure (AUC =0.847, 95% CI: 0.733-0.961; P<0.001). Conclusions: In PH, TV geometric remodeling occurs mainly in TA septal-lateral dimension and TV tenting height. Worsening PH is an independent determinant of TV coaptation point height and MTH, not TA size. MTH shows a great diagnostic potential to detect severe PH.

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT.

BACKGROUND: The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood-brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials. METHODS: Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes. RESULTS: 86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17-0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05-0.92; p = .015). CONCLUSIONS: EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers.

Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types of cancer. However, the widespread use of ICIs has brought about a number of safety concerns, especially the development of immune-related adverse events (irAEs). These serious complications could result in treatment discontinuation and even life-threatening consequences, making it critical to identify high-risk groups and predictive markers of irAEs before initiating therapy. To this end, the current article examines several potential predictive markers of irAEs in important organs affected by ICIs. While retrospective studies have yielded some promising results, limitations such as small sample sizes, variable patient populations, and specific cancer types and ICIs studied make it difficult to generalize the findings. Therefore, prospective cohort studies and real-world investigations are needed to validate the potential of different biomarkers in predicting irAEs risk. Overall, identifying predictive markers of irAEs is a crucial step towards improving patient safety and enhancing the management of irAEs. With ongoing research efforts, it is hoped that more accurate and reliable biomarkers will be identified and incorporated into clinical practice to guide treatment decisions and prevent the development of irAEs in susceptible patients.