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PURPOSE The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.

Lung cancer is one of the most threatening diseases to human life and health because of its mortality. How to choose more efficient drugs and the appropriate timing of treatment for patients with advanced lung cancer is still a problem. As the urine proteome can sensitively reflect the pathological or physiological changes of the body, it has the potential to reflect the dynamic changes of the body after drug treatment. To investigate the changes in the urine proteome of patients with advanced lung cancer after different drug treatments, urine samples were collected and analyzed at different time points. The changes in the urine proteome from the pretreatment state were different in each patient, although some of them were treated with the same drugs. The changes in the biological processes reflected by the differential urinary proteins were consistent with the changes in the clinical manifestations of the patients. This study demonstrates that the pathophysiological changes of patients with advanced lung cancer can be reflected by changes in urinary protein after different drug treatments. In addition, the changes in urinary proteins can reflect the different biological processes in patients after the same drug treatment, and the patients’ clinical condition assessment results are consistent with these changes. These findings may provide additional information for clinical treatment.

Glioblastoma (GBM) is the most lethal primary brain tumor in adults and harbors a subpopulation of glioma stem cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), a histone lysine methyltransferase, deeply involves in the stemness maintenance of GSC. However, the precise mechanism and therapeutic potential remain elusive. We postulated that the interactome of EZH2 in GSC is unique. Therefore, we performed proteomic and transcriptomic research to unveil the oncogenic mechanism of EZH2. Immunoprecipitation and mass spectrometry were used to identify proteins that co-precipitate with EZH2. We show that EZH2 binds to heterochromatin protein 1 binding protein 3 (HP1BP3) in GSCs and impairs the methylation of H3K9. Overexpression of HP1BP3 enhances the proliferation, self-renewal and temozolomide (TMZ) resistance of GBM cells. Furthermore, EZH2 and HP1BP3 co-activate WNT7B expression thereby increasing TMZ resistance and stemness of GBM cells. Importantly, inhibition of WNT7B autocrine via LGK974 effectively reverses the TMZ resistance. Our work clarifies a new oncogenic mechanism of EZH2 by which it interacts with HP1BP3 and epigenetically activates WNT7B thereby promoting TMZ resistance in GSCs. Our results provide a rationale for targeting WNT/β-catenin pathway as a promising strategy to overcome TMZ resistance in GSCs.

This study evaluated the role of miRNA-1592 (miR-1592) carried by exosomes that originated from bone marrow mesenchymal stem cell (BMSC) in glioma. BMSCs were cultured and identified, followed by being co-cultured with glioma cells to measure cell invasion, metastasis, and apoptosis by transwell assay and flow cytometry, cell proliferation by MTT, PI3K/AKT signal protein expression by western blot. BMSC-originated exosomes with different concentrations were used as a treatment strategy for established tumor models. The tumor volume was measured and tumor tissues were harvested for immunohistochemistry and immunoblot analysis. After co-culture with BMSC-originated exosomes, glioma cells showed an up-regulated transcription of miR-1592, along with inhibited phosphorylation and activation of PI3K/AKT signal pathway. Moreover, glioma cells exhibited reduced migration and invasiveness In Vitro, which was accompanied by diminished levels of proteins involved in cellular invasiveness. Simultaneously, co-culture with BMSC-originated exosomes can restrain glioma cell proliferation via facilitating cell apoptosis In Vivo and In Vitro. In conclusion, exosome-encapsulated microRNA-1592 from BMSCs can suppress the In Vivo and In Vitro development of glioma through interfering with PI3K/AKT signaling pathway.

During embryo development, DNA methylation is established by DNMT3A/3B and subsequently maintained by DNMT1. While much research has been done in this field, the functional significance of DNA methylation in embryogenesis remains unknown. Here, we establish a system of simultaneous inactivation of multiple endogenous genes in zygotes through screening for base editors that can efficiently introduce a stop codon. Embryos with mutations in Dnmts and/or Tets can be generated in one step with IMGZ. Dnmt-null embryos display gastrulation failure at E7.5. Interestingly, although DNA methylation is absent, gastrulation-related pathways are down-regulated in Dnmt-null embryos. Moreover, DNMT1, DNMT3A, and DNMT3B are critical for gastrulation, and their functions are independent of TET proteins. Hypermethylation can be sustained by either DNMT1 or DNMT3A/3B at some promoters, which are related to the suppression of miRNAs. The introduction of a single mutant allele of six miRNAs and paternal IG-DMR partially restores primitive streak elongation in Dnmt-null embryos. Thus, our results unveil an epigenetic correlation between promoter methylation and suppression of miRNA expression for gastrulation and demonstrate that IMGZ can accelerate deciphering the functions of multiple genes in vivo.

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes.MethodsWe retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry.ResultsPatients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/μL, p < 0.001). Using 190/μL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/μL.ConclusionsHigh circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/μL) may also indicate the emergence of severe irAEs.

As rare ginsenosides, 20(R, S)-ginsenoside Rh1 [20(R, S)-Rh1] are isomers and have been reported to exhibit multiple biological effects. However, the application of 20(R, S)-Rh1 is still limited due to their poor solubilities and low bioavailabilities. Here, the complexation mechanism between 20(R, S)-Rh1 and serum albumin (SA) was explored by a combination of multi-spectroscopy and in silico investigations. Results of spectra experiments showed that 20(R, S)-Rh1 could form complexes with bovine serum albumin (BSA) and quench its intrinsic fluorescence. In addition, the influence of BSA on the anti-cancer activity of 20(R, S)-Rh1 was also evaluated in A549 cells. The result of the MTT assay indicated that anti-cancer activity of 20(R, S)-Rh1 was enhanced when combined with BSA. The results of molecular docking and dynamics simulation demonstrated that the subtle structural differences of 20(R, S)-Rh1 at the 20-carbon atom may be responsible for their different binding capacities and binding stabilities with human serum albumin. The cytotoxicity assay for 20(R, S)-Rh1 alone and their complexes with BSA demonstrated the enhancement effect of BSA for inhibition of cell proliferation. In conclusion, this work provided insight into the complexation mechanism between 20(R, S)-Rh1 and SA. PRACTICAL APPLICATION: The complexation mechanism between 20(R, S)-ginsenoside Rh1 [20(R, S)-Rh1] and serum albumin (SA) was explored by a combination of multi-spectroscopy and in silico investigations in this work. The cytotoxicity assay for 20(R, S)-Rh1 alone and their complexes with bovine serum albumin (BSA) demonstrates the enhancement effect of BSA for inhibition of cell proliferation. Hence, this work provided insight into the complexation mechanism between 20(R, S)-Rh1 and SA.

Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2+/35delG and Gjb2+/235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P)28. A homozygous mutant mouse model, Gjb235delG/35delG, was then generated using enhanced tetraploid embryo complementation, demonstrating that GJB2 plays an indispensable role in mouse placenta development. These mice exhibited profound hearing loss similar to human patients at P14, i.e., soon after the onset of hearing. Mechanistic analyses showed that Gjb2 35delG disrupts the formation of intercellular gap junction channels and impairs mechanoelectrical transduction of the cochlea rather than affecting the survival and function of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism of DFNB1A-related hereditary deafness and opens up a new avenue for investigating the treatment of this disease.

Purpose Approximately 1/3 of brain tumors are gliomas. Previous glioma-related studies have reported increased expression of periostin (POSTN) in these cancerous tissues, but the role and mechanism of POSTN in glioma development remain unclear. Methods Nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC–MS/MS) and RNA sequencing were used to identify differential protein and mRNA expression in clinical glioma samples. Quantitative real-time PCR (qRT–PCR) was used to measure the expression of POSTN in tissues and cells. The effects of POSTN on glioma cell migration and invasion were examined using wound healing, Transwell, and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo. The effects of POSTN on the stability, endocytosis, and degradation of EGFR were examined by immunoblotting and immunofluorescence staining. Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR. Immunohistochemical staining was carried out to confirm the clinical significance of POSTN. Results Overexpression of POSTN induced epithelial-to-mesenchymal transition (EMT) in glioma cells in vivo and in vitro. Mechanistically, POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation. In addition, POSTN was found to bind to EGFR and RIN1, inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway. Conclusion These findings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation, resulting in glioma cell EMT through the PI3K-AKT signaling pathway. Targeting POSTN/EGFR/RIN1 interactions may guarantee beneficial outcomes of glioma treatment.

The MnO2-based aqueous Zn cell can meet the requirements of safety, flexibility, and low cost for portable/wearable electronics; however, its low intrinsic conductivity, weak kinetics, and poor high-loading capacity restrict its practical performance. In this study, the synergistic architecture of MoS2-loaded, oxygen-defect-rich MnO2-x nanocrystals with a carbon coating (M-PM2-x-H2 aerogel) was prepared. As corevealed by various characterizations, this synergistic design not only improves the electronic/ionic conductivity but also motivates the conversion kinetics of the surficial electrochemical reaction. As a result, the M-PM2-x-H2 cathode delivers a much improved capacity of 567 mA h·g-1 at 0.1 A·g-1 and shows a high capacity retention of 176% after 150 cycles at 0.5 A·g-1. More impressively, the high areal loading (3.97 mg·cm-1) of the M-PM2-x-H2 electrode also displays a high capacity of 367 mA h·g-1 at 0.1 A·g-1. In addition, the derived all-solid-state cell exhibits excellent flexibility and safety under the conditions of weight loading, cutting, and bending.

Radioactive iodine, one type of nuclear waste, is harmful to the environment and human health due to its long half-life and volatility. Therefore, designing and synthesizing low-cost and easily-made materials for the effective adsorption of radioiodine is widely concerned. Herein, a biscuit-shaped new material was synthesized by a grinding-mixing coupled with sonication protocol through self-assembly interactions between citrazinic acid (CA) and cytosine (CY) aiming to achieve the iodine capture from both vapor and solution. Electronic structure calculations were used to reveal the adsorption mechanism. The results showed that the high uptake of iodine by CACY originates from the charge transfer via CACY to the antibonding molecular orbital (σ∗) of I2. Meanwhile, trouble-free entry pore sizes of CACY also contribute to the physisorption of molecular iodine. Besides, the iodine molecule is preferentially perpendicularly adsorbed on the carbon atom of the CA ring. Moreover, CACY exhibits a high capture for iodine in hexane following pseudo-second-order kinetics and fitting the Langmuir isotherm model. This work presents a facile and inexpensive synthesis approach for radioiodine adsorption materials and provides new insights into the interaction mechanism between the self-assembled materials and the adsorbates.

Background Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanism is unclear. Purpose To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. Methods We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. Results The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient hyperthyroidism), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to onset was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29–0.67; P

Correction for ‘Novel anilino quinazoline-based EGFR tyrosine kinase inhibitors for treatment of non-small cell lung cancer’ by Lili Yang et al., Biomater. Sci., 2021, 9, 443–455. DOI: 10.1039/D0BM00293C.

The advancement in flexible electronics and neuromorphic electronics has opened up opportunities to construct artificial perception systems to emulate biological functions which are of great importance for intelligent robotics and human-machine interactions. However, artificial systems that can mimic the somatosensory feedback functions have not been demonstrated yet despite the great achievement in this area. In this work, inspired by human somatosensory feedback pathways, an artificial somatosensory system with both perception and feedback functions was designed and constructed by integrating the flexible tactile sensors, synaptic transistor, artificial muscle, and the coupling circuit. Also, benefiting from the synaptic characteristics of the designed artificial synapse, the system shows spatio-temporal information-processing ability, which can further enhance the efficiency of the system. This research outcome has a potential contribution to the development of sensor technology from signal sensing to perception and cognition, which can provide a special paradigm for the next generation of bionic tactile perception systems towards e-skin, neurorobotics, and advanced bio-robots.

BackgroundPulmonary lymphoepithelioma-like carcinoma (LELC) exhibits a unique immune microenvironment, including high PD-L1 expression and abundant infiltrating-immune cells. However, the availability of PD-1/PD-L1 inhibitors in patients with LELC is still not determined.MethodsA total of 36 cases of pulmonary LELC treated with PD-1/PD-L1 inhibitors were reviewed, including 10 cases from our institute and 26 cases included from the literature. The Kaplan-Meier method and log-rank test were utilized to analyze the survival outcomes of LELC patients receiving immunotherapy, and the factors related to immunotherapy response were further examined.ResultsOf the 10 patients from our institute, the median age was 53.5 years, adrenal glands and distant lymph nodes were the most common metastatic sites, and 4 of 8 (50%) patients had a PD-L1 TPS ≥50%. The median progression-free survival and overall survival in patients from our institute and from the literature were 11.6 and 27.3 months, 17.2 months and not reached, respectively. In all 36 patients, the objective response rate was as high as 57.6%. Patients with higher PD-L1 expression were more likely to have a tumor response, but the association of PD-L1 expression with survival time remains to be determined.ConclusionsPD-1/PD-L1 inhibitors in patients with pulmonary LELC demonstrated a promising efficacy in retrospective cohorts, and deserve further validation in prospective studies administrating in front-line setting.

S-1 has been recognized as one of the standard adjuvant chemotherapies for pancreatic ductal adenocarcinoma (PDAC) in East Asia, but the optimal adjuvant chemotherapy regimen has not been determined. We aimed to compare the efficacy and safety of adjuvant gemcitabine plus S-1 (GS) with S-1 monotherapy for PDAC.Patients with resected PDAC who received adjuvant GS or S-1 chemotherapy in Peking Union Medical College Hospital between May 2014 and May 2022 were reviewed. Data retrieved from medical records were used to evaluate efficacy and toxicity.A total of 241 patients were included, with 167 receiving GS and 74 receiving S-1. The patients who received GS were generally younger (median [range] age: 62 [36-78] versus 64 [44-87] years, p = 0.004), but chemotherapy began later (median [range] interval between chemotherapy and surgery: 49 [17-125] versus 40 [16-100] days, p0.001). The median disease-free survival (DFS, 15.1 versus 15.9 months, p = 0.52) and overall survival (OS, 34.8 versus 27.1 months, p = 0.34) did not differ significantly between the GS and S-1 groups, even after adjustment for the biases. However, the chemotherapy completion rate was higher in the patients treated with S-1 (52.4% versus 75.7%, p = 0.006), while grade 3-4 neutropenia occurred more frequently in the GS group (49.5% versus 18.2%, p = 0.015).Adjuvant S-1 monotherapy demonstrated noninferiority to the GS regimen in DFS and OS with better tolerability for PDAC following surgery.

A tactile sensor system enables natural interaction between humans and machines; this interaction is crucial for dexterous robotic hands, interactive entertainment, and other smart scenarios. However, the lack of sliding friction detection significantly limits the accuracy and scope of interactions due to the absence of sophisticated information, such as slippage, material and roughness of held objects. Here, inspired by the stick-slip phenomena in the sliding process, we have developed a multifunctional biomimetic tactile system based on the stick-slip sensing strategy, which is a universal method to detect slippage and estimate the surface properties of objects by sliding. This system consists of a flexible fingertip-inspired tactile sensor, a read-out circuit and a machine-learning module. Based on the stick-slip sensing strategy, our system was endowed with high recognition rates for slippage detection (100.0%), material classification (93.3%) and roughness discrimination (92.8%). Moreover, robotic hand manipulation, interactive games and object classification are demonstrated with this multifunctional system for comprehensive and promising human–machine interactions.

ObjectiveThis paper studies the impact of the subjective life expectancy of the elderly on their commercial pension insurance participation at micro perspective, providing new evidence to explain the motivation of commercial pension insurance participation in China.MethodsUsing 4 waves of data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, a multiple linear regression model is constructed to investigate the effect of subjective life expectancy on commercial pension insurance participation among the Chinese elderly, and IV model estimation shows that the results are robust. Meanwhile, the heterogeneity of the effect of elderly life expectancy on commercial pension insurance participation behavior among different characteristic groups is also studied.ResultsA one standard deviation improvement in our measure of subjective life expectancy predicts a 0.9% point higher participation rate in commercial pension insurance. We also find that there is significant heterogeneity in the effects of subjective life expectancy on the participation of elderly people in commercial pension insurance with respect to gender, education, hukou, and wealth.ConclusionThis paper provides a new perspective to explain the factors influencing commercial pension insurance participation in China. We suggest that improving residents’ awareness of life expectancy is beneficial to their reasonable retirement planning, in the background of stepping into an aging society in China.

Background We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer. Methods A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival. Result Patients were classified into 4-level score groups (score 1–4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15–0.48, P Conclusion The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.

Imbuing artificial sensory system with intelligence of the biological counterpart is limited by challenges in emulating perceptual learning ability at the device level. In biological systems, stimuli from the surrounding environment are detected, transmitted, and processed by receptor, afferent nerve, and brain, respectively. This process allows the living creatures to identify the potential hazards and improve their adaptability in various environments. Here, inspired by the biological olfaction system, a gas sensory system with perceptual learning is developed. As a proof-of-concept, H2S gas with various concentrations is used as the stimulation and the stimuli will be converted to pulse-like physiological signals in the designed system, which consists of a gas sensor, a flexible oscillator, and a memristor-type artificial synapse. Furthermore, the learning ability is implemented using a supervised learning method based on k-nearest neighbors (KNN) algorithm. The recognition accuracy can be enhanced by repeating training, illustrating a great potential to be used as the neuromorphic sensory system with a learning ability for the applications in robotics.

This article mainly analyzes the clinical effects of magnetic resonance diagnosis in knee meniscus injury. Patients with knee meniscus injury were taken as the research object. All patients used magnetic resonance examination and surgery and arthroscopy examination, and surgery and arthroscopy examination as the control parameters. The analysis used magnetic resonance diagnosis results and the classification of meniscus injury diagnosed by magnetic resonance and surgery and arthroscopy. The results showed that the sensitivity, specificity, and accuracy of conventional MR1 sequence diagnosis of medial meniscus injury were 86.3%, 95.6%, and 92.4%, respectively. The sensitivity, specificity and accuracy of conventional MRI in diagnosing lateral meniscus injury of the knee joint were 91.3%, 94.5%, and 92.5% respectively. The sensitivity of MRI to medial and lateral meniscus injury was (χ2 = 0.07, P > 0.77), There were no significant differences in specificity χ2 = 0.01, P > 0.77) and accuracy χ2 = 0.01, P > 0.77). The knee meniscus injury has a greater impact on patients. The diagnostic effect of magnetic resonance imaging is better and the diagnostic accuracy is higher. It can help clinical judgment and treatment. The effect is obvious and worthy of clinical promotion.

Jingzhaotoxin-I, -III, -IV, -XIII, and −35 (JZTX-I, -III, -IV, -XIII, and −35), gating modifier toxins isolated from the venom of the Chinese tarantula Chilobrachys Jingzhao, were reported to act on cardiac sodium channels and Kv channels. JZTX-I and JZTX-XIII inhibited the hERG channel with the IC50 value of 626.9 nM and 612.6 nM, respectively. JZTX-III, -IV, and −35 share high sequence similarity with JZTX-I and JZTX–XIII, but they showed much lower affinity on the hERG channel compared with JZTX-I and JZTX-XIII. The inhibitory potency of the above five toxins on the hERG channel was not in accordance with their affinity on the Nav1.5 and Kv2.1 channels, indicating that the bioactive surfaces of the five toxins interacting with hERG, Nav1.5 and Kv2.1 are at least in part different. Structure-function analysis of the gating modifier toxins suggested that the functional bioactive surface binding to the hERG channel consists of a conserved hydrophobic patch, surrounding acidic residues (Glu10 in JZTX-XIII, Glu11 in JZTX-I), and basic residues which may be different from residues binding to the Kv2.1 channel.

Objective The Immunoscore method has proved fruitful for predicting prognosis in patients with colon cancer. However, there is still room for improvement in this scoring method to achieve further advances in its clinical translation. This study aimed to develop and validate a modified Immunoscore (IS-mod) system for predicting overall survival (OS) in patients with stage I-III colon cancer. Methods The IS-mod was proposed by counting CD3+ and CD8+ immune cells in regions of the tumor core and its invasive margin by drawing two lines of interest. A discovery cohort (N=212) and validation cohort (N=103) from two centers were used to evaluate the prognostic value of the IS-mod. Results In the discovery cohort, 5-year survival rates were 88.6% in the high IS-mod group and 60.7% in the low IS-mod group. Multivariate analysis confirmed that the IS-mod was an independent prognostic factor for OS [adjusted hazard ratio (HR)=0.36, 95% confidence interval (95% CI): 0.20-0.63]. With less annotation and computation cost, the IS-mod achieved performance comparable to that of the Immunoscore-like (IS-like) system (C-index, 0.676 vs. 0.661, P=0.231). The 2-category IS-mod using 47.5% as the threshold had a better prognostic value than that using a fixed threshold of 25% (C-index, 0.653 vs. 0.573, P=0.004). Similar results were confirmed in the validation cohort. Conclusions Our method simplifies the annotation and accelerates the calculation of Immunoscore method, thus making it easier for clinical implementation. The IS-mod achieved comparable prognostic performance when compared to the IS-like system in both cohorts. Besides, we further found that even with a small reference set (N≥120), the IS-mod still demonstrated a stable prognostic value. This finding may inspire other institutions to develop a local reference set of an IS-mod system for more accurate risk stratification of colon cancer.

Recent studies have reported the crucial role of stanniocalcin-2 (STC2) in hepatocellular carcinoma; however, its role in head and neck squamous cell carcinoma (HNSCC) remains elusive. In this study, microRNA-206 (miR-206) was predicted to target STC2 gene. The study herein aimed to elucidate the effect of miR-206 on HNSCC by targeting STC2. STC2 was highly expressed in HNSCC tissues and cells. By targeting STC2, miR-206 decreased mRNA and protein expression of STC2. Importantly, our study showed that miR-206 blocked the Akt signaling pathway by inhibiting STC2. Intriguingly, our data from in vitro and in vivo experiments suggested that miR-206 overexpression led to decreased cell proliferation and increased cell apoptosis and autophagy, as well as suppressed tumor growth; whereas, STC2 silencing reversed the effects of miR-206 inhibitor on those biological behaviors. In this study, we investigated the antioncogenic effect of miR-206 on HNSCC by targeting STC2, and highlighted miR-206/STC2 aixs as potential therapeutic targets for HNSCC.

Background: Accumulating evidence has suggested that the extracellular matrix (ECM) plays a vital role in the development and progression of cancer, and could be recognized as a biomarker of the response to immunotherapy. However, the effect of the ECM signature in hepatocellular carcinoma (HCC) is not well understood.Methods: HCC patients derived from the TCGA-LIHC dataset were clustered according to the ECM signature. The differences in prognosis, functional enrichment, immune infiltration, and mutation characteristics between distinct molecular clusters were examined, and its predictive value on the sensitivities to chemotherapy and immunotherapy was further analyzed. Then, a prognostic model was built based on the ECM-related gene expression pattern.Results: HCC patients were assigned into two molecular subtypes. Approximately 80% of HCC patients were classified into cluster A with poor prognosis, more frequent TP53 mutation, and lower response rate to immunotherapy. In contrast, patients in cluster B had better survival outcomes and higher infiltration levels of dendritic cells, macrophages, and regulatory T cells. The prognostic risk score model based on the expression profiles of six ECM-related genes (SPP1, ADAMTS5, MMP1, BSG, LAMA2, and CDH1) demonstrated a significant association with higher histologic grade and advanced TNM stage. Moreover, the prognostic risk score showed good performance in both the training dataset and validation dataset, as well as improved prognostic capacity compared with TNM stage.Conclusions: We characterized two HCC subtypes with distinct clinical outcomes, immune infiltration, and mutation characteristics. A novel prognostic model based on the ECM signature was further developed, which may contribute to individualized prognostic prediction and aid in clinical decision-making.

Neuroinflammation is closely related to the pathogenesis of perioperative neurocognitive disorders (PNDs), which is characterized by the activation of microglia, inflammatory pathways and the release of inflammatory mediators. Sigesbeckia orientalis L. (SO) is a traditional Chinese medicine which demonstrates anti-inflammatory activities in different models. In this study, we aim to isolate the active fraction from the extract of SO with higher anti-inflammatory potential and confirm if the selected fraction exerts neuroprotection against the development of PND in an animal model. Moreover, the components in the selected fraction would be determined by UPLC-PDA analysis. Three fractions were prepared by column chromatography packed with three different macroporous resins. Anti-inflammatory activities of prepared fractions were accessed in microglial BV2 cultures by nitric oxide release, gene expression of inflammatory cytokines and activation of inflammatory JNK and NF-kB pathway molecules. Our results demonstrated that the fraction prepared from D101 macroporous resin (D101 fraction) exhibited a more potent anti-neuroinflammatory effect. The neuroprotective effect of D101 fraction was further examined in postoperative mice. Our results showed that surgery-induced cognitive dysfunction was attenuated by the D101 fraction treatment. This fraction also reduced microglial activation, inflammatory cytokines and inhibiting JNK and NF-kB pathway molecules in the hippocampus. In addition, surgery induced dendritic spine loss while D101 fraction ameliorated the spine loss in the hippocampus. For safety concerns, anti-thrombotic effect was examined by tail bleeding assay and no significant change of the bleeding pattern was found. UPLC-PDA analysis indicated that flavonoids (rutin, isochlorogenic acid A, isochlorogenic acid C) and terpenoid (darutoside) were the most important components in the D101 fraction. Our results support a therapeutic, as well as the translational potential for D101 fraction in ameliorating postoperative neuroinflammation and subsequent PND in the clinical setting without increasing bleeding tendencies.

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood.MethodsThe present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed.Results67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS.ConclusionsThe presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

Purpose We aimed to develop a nomogram for predicting the prognosis of patients with distal cholangiocarcinoma (DCC) and to compare its performance with that of the American Joint Committee on Cancer (AJCC) TNM system. Patients and Methods To develop a nomogram, we collected the clinical data of 147 patients diagnosed with DCC who underwent pancreatoduodenectomy. Predictive accuracy and discriminative ability were determined using a concordance index and a calibration curve. Predictive performance was compared with that of a current staging systems for DCC. Results Multivariate analysis revealed that jaundice, alcohol consumption, high fibrinogen, poorly differentiated tumor cells, positive lymph nodes, and positive margins were significantly associated with overall survival. These variables were incorporated into the nomogram. The concordance index of the nomogram for predicting overall survival was 0.737 (P

Rationale and Objectives To evaluate the noninvasive predictive performance of deep learning features based on staging CT for sentinel lymph node (SLN) metastasis of breast cancer. Materials and Methods A total of 348 breast cancer patients were enrolled in this study, with their SLN metastases pathologically confirmed. All patients received contrast-enhanced CT preoperative examinations and CT images were segmented and analyzed to extract deep features. After the feature selection, deep learning signature was built with the selected key features. The performance of the deep learning signatures was assessed with respect to discrimination, calibration, and clinical usefulness in the primary cohort (184 patients from January 2016 to March 2017) and then validated in the independent validation cohort (164 patients from April 2017 to December 2018). Results Ten deep learning features were automatically selected in the primary cohort to establish the deep learning signature of SLN metastasis. The deep learning signature shows favorable discriminative ability with an area under curve of 0.801 (95% confidence interval: 0.736–0.867) in primary cohort and 0.817 (95% confidence interval: 0.751–0.884) in validation cohort. To further distinguish the number of metastatic SLNs (1–2 or more than two metastatic SLN), another deep learning signature was constructed and also showed moderate performance (area under curve 0.770). Conclusion We developed the deep learning signatures for preoperative prediction of SLN metastasis status and numbers (1–2 or more than two metastatic SLN) in patients with breast cancer. The deep learning signature may potentially provide a noninvasive approach to assist clinicians in predicting SLN metastasis in patients with breast cancer.

Jiayi Li, 1,* Qiao Chen, 1,* Bao Jin, 1 Yue Shi, 1 Xiangan Wu, 1 Haifeng Xu, 1 Yongchang Zheng, 1 Yingyi Wang, 2 Shunda Du, 1 Xin Lu, 1 Yilei Mao, 1 Xinting Sang 1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunda DuDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai-Fu-Yuan, Wang-Fu-Jing, Beijing 100730, People’s Republic of ChinaTel +86-139 1183 2900Fax +86-10-69156043Email dushd@pumch.cnPurpose: The aims of our study were to investigate the prognostic impact of the rate of preoperative serum carbohydrate antigen 19-9/bilirubin (CA19-9/BR) on patients with extrahepatic bile duct cancer.Patients and Methods: We collected clinical data from 89 patients who underwent surgery for extrahepatic cholangiocarcinoma (ECC) at Peking Union Medical College Hospital between January 2012 and December 2017. The Kaplan–Meier analysis for univariate analysis and the Cox proportional hazards models for multivariate analysis were used to determine possible independent prognostic factors.Results: CA19-9/BR was classified as elevated compared with normal based on the upper serum normal values of CA19-9 (37 U/mL) and bilirubin (1.5 mg/dL), which gives a cut-off at 25 U/mL/mg/dL. Univariate analysis showed that the overall survival of patients with a high CA19-9/BR ratio was significantly worse compared with patients with a low CA19-9/BR ratio (Hazard Ratio [HR] 2.149; 95% Confidence Interval [95% CI] 1.027– 4.495; P=0.042). Multivariate analysis revealed that a high CA19-9/BR ratio (HR 3.250; 95% CI 1.165– 9.067; P=0.024), low differentiation (HR 3.551; 95% CI 1.231– 10.244; P=0.019), and positive margin (HR 2.555; 95% CI 1.111– 5.875; P=0.027) remained independent prognostic factors after adjusting for age at diagnosis, maximal diameters, and other possible factors.Conclusion: The preoperative CA19-9/BR ratio is a good prognostic factor in predicting survival in ECC patients and closer follow-up is recommended in patients with a higher CA19-9/BR ratio before surgery.Keywords: prognosis, preoperative bilirubin-adjusted carbohydrate antigen 19-9, extrahepatic cholangiocarcinoma

The glioma immune microenvironment (GIM), consisting of glioma cells, stromal cells, and immune cells, accelerates the initiation, development, immune evasion, chemoresistance, and radioresistance of glioblastoma (GBM), whereas the immunosuppressive mechanisms of GBM have not been thoroughly elucidated to date. The glioma data downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to evaluate the composition of tumor-infiltrating immune cells (TICs) by the CIBERSORT algorithm. RNA-seq datasets from the TCGA and CGGA were used to analyze the relationship between immune scores with patients’ characteristics and TICs, which showed higher ratios of tumor-inhibiting/tumor-promoting signatures (M2/M1 macrophages) along with higher immune scores. The distribution of TICs among different glioma patients and the correlation with hazard ratio (HR) analysis suggested that M2 macrophages were abundant in malignant gliomas and indicated an unfavorable prognosis. We further analyzed TCGA cases with available mutation and copy-number alteration information, which showed that the status of PTEN could influence the immune microenvironment of glioma patients. Tissue microarrays of 39 GBM patients were carried out to confirm the clinical significance of PTEN and macrophage markers. We found that the high expression of PTEN was associated with a more extended survival period of glioma patients, positively correlated with M2 macrophages and negatively with M1 macrophages. Transwell and flow cytometry analyses demonstrated that PTEN status could prevent M1 to M2 polarization and M2 macrophage recruitment of gliomas in vitro. The newly discovered immunoregulatory activity of PTEN opens innovative avenues for investigations relevant to counteracting cancer development and progression.

Jiayi Li,1,2,&ast; Qiao Chen,1,3,&ast; Lei Guo,4,&ast; Ji Li,5 Bao Jin,1 Xiangan Wu,1 Yue Shi,1 Haifeng Xu,1 Yongchang Zheng,1 Yingyi Wang,6 Shunda Du,1 Zhili Li,4 Xin Lu,1 Xinting Sang,1 Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 4Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China; 5Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 6Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Du; Zhili Li, Email dushd@pumch.cn; lizhili@ibms.pumc.edu.cnPurpose: To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification.Patients and Methods: We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student’s t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set.Results: Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4&ast;[m/z 436.2834] - 3.773&ast;[m/z 474.2626] + 3.82&ast;[m/z 661.4813] - 4.394&ast;[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985– 0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II.Conclusion: We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification.Keywords: intrahepatic cholangiocarcinoma, in situ lipids profiles, metabolomics, mass spectrometry, classification and diagnostic model

Background: Lepidic adenocarcinoma (LPA) is an infrequent subtype of invasive pulmonary adenocarcinoma (ADC). However, the clinicopathological features and prognostic factors of LPA have not been elucidated.Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database of 4087 LPA patients were retrospectively analyzed and compared with non-LPA pulmonary ADC to explore the clinicopathological and prognosis features of LPA. Univariate and multivariate Cox proportional hazard models were performed to identify independent survival predictors for further nomogram development. The nomograms were validated by using the concordance index, receiver operating characteristic curves, and calibration plots, as well as decision curve analysis, in both the training and validation cohorts.Results: Compared with non-LPA pulmonary ADC patients, those with LPA exhibited unique clinicopathological features, including more elderly and female patients, smaller tumor size, less pleural invasion, and lower histological grade and stage. Multivariate analyses showed that age, sex, marital status, primary tumor size, pleural invasion, histological grade, stage, primary tumor surgery, and chemotherapy were independently associated with overall survival (OS) and cancer-specific survival (CSS) in patients with LPA, while race was the only independent prognostic factor for OS, not for CSS. The nomograms showed good accuracy compared with the actual observed results and demonstrated improved prognostic capacity compared with TNM stage.Conclusions: Patients with LPA are more likely to be older and female. Smaller tumor size, lower histological grade and stage are the clinicopathological features of LPA, which may indicate a good prognosis. The constructed nomograms accurately predict the long-term survival of LPA patients.

For the energy supply of smart and portable equipment, high performance supercapacitor electrode materials are drawing more and more concerns. Conductive Ni-MOF is a class of materials with higher conductivity compared with traditional MOFs, but it continues to lack stability. Specifically, MXene (Ti3C2Tx) has been employed as an electrochemical substrate for its high mechanical stability and abundant active sites, which can be combined with MOFs to improve its electrochemical performance. In this paper, a novel Ni-MOF nanorods array/Ti3C2Tx nanocomposite was prepared via a facile hydrothermal reaction, which makes good use of the advantages of conductive Ni-MOF and high strength Ti3C2Tx. The high density forest-like Ni-MOF array in situ grown on the surface of Ti3C2Tx can provide abundant active electrochemical sites and construct a pathway for effective ion transport. The formation of a “Ti-O···Ni” bond accomplished during an in situ growth reaction endows the strong interfacial interaction between Ni-MOF and Ti3C2Tx. As a result, the Ni-MOF/Ti3C2Tx nanocomposite can achieve a high specific capacitance of 497.6 F·g−1 at 0.5 A·g−1 and remain over 66% of the initial capacitance when the current density increases five times. In addition, the influence of the Ti3C2Tx concentration and reaction time on the morphology and performance of the resultant products were also investigated, leading to a good understanding of the formation process of the nanocomposite and the electrochemical mechanism for a supercapacitive reaction.

The development of high-performance, portable and miniaturized gas sensors has aroused increasing interest in the fields of environmental monitoring, security, medical diagnosis, and agriculture. Among different detection tools, metal oxide semiconductor (MOS)-based chemiresistive gas sensors are the most popular choice in commercial applications and have the advantages of high stability, low cost, and high sensitivity. One of the most important ways to further enhance the sensor performance is to construct MOS-based nanoscale heterojunctions (heteronanostructural MOSs) from MOS nanomaterials. However, the sensing mechanism of heteronanostructural MOS-based sensors is different from that of single MOS-based gas sensors in that it is fairly complex. The performance of the sensors is influenced by various parameters, including the physical and chemical properties of the sensing materials (e.g., grain size, density of defects, and oxygen vacancies of materials), working temperatures, and device structures. This review introduces several concepts in the design of high-performance gas sensors by analyzing the sensing mechanism of heteronanostructural MOS-based sensors. In addition, the influence of the geometric device structure determined by the interconnection between the sensing materials and the working electrodes is discussed. To systematically investigate the sensing behavior of the sensor, the general sensing mechanism of three typical types of geometric device structures based on different heteronanostructural materials are introduced and discussed in this review. This review will provide guidelines for readers studying the sensing mechanism of gas sensors and designing high-performance gas sensors in the future.

Food contamination and poisoning caused by bacteria will endanger human health, and the development of natural antibacterial agents is a pressing issue. We prepared ALA-Car complex and demonstrated its formation by multi-spectroscopy techniques and localized surface plasmon resonance experiments. Computer simulations have shown that van der Waals forces dominate the interaction between ALA and Car. The minimum inhibitory concentration (MIC) of Car toward Gram-negative Escherichia coli was decreased from 336 μg/mL to 224 μg/mL after binding to ALA. It had little effect on the MIC of Gram-positive Staphylococcus aureus (224 μg/mL), but further proved Car had a weaker antibacterial activity than the ALA-Car complex by the spread plate method. Overall, this work demonstrated that the ALA-Car complex had significantly higher antibacterial activities than Car, further advancing the development of natural antibacterial agents.

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC. .【中文题目：EGFR突变非小细胞肺癌患者奥希替尼诱导间质性肺疾病后奥希替尼再挑战：病例报道】 【中文摘要：奥希替尼诱导的间质性肺疾病（interstitial lung disease, ILD）是一种罕见的、致命的肺毒性疾病。我们报道1例64岁男性IV期肺腺癌患者，伴有表皮生长因子受体（epidermal growth factor receptor, EGFR）外显子19缺失，使用奥希替尼80 mg/d作为一线靶向治疗。奥希替尼开始治疗后第60天患者出现ILD。立即停用奥希替尼，并开始口服泼尼松60 mg/d，ILD在13 d内得到改善。权衡风险和获益后，再次开始奥希替尼与泼尼松治疗。奥希替尼治疗16个月以上，患者既没有疾病进展，也没有ILD复发。根据我们的病例和既往文献，在仔细评估EGFR突变非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的风险及获益后，在类固醇激素辅助下再次使用奥希替尼可被视为一种有效的治疗选择。 】 【中文关键词：表皮生长因子受体；间质性肺疾病；肺肿瘤；奥希替尼】.

The MnO

Heterostructured metal oxides with large specific surface area are crucial for constructing gas sensors with high performance. However, using slurry-coating and screen-printing methods to fabricate...

Background Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two key protein-bound uremic toxins that accumulate in patients with end-stage renal disease. IS and pCS cannot be efficiently removed by conventional hemodialysis because they are highly bound to proteins. One promising means to optimize the removal of protein-bound uremic toxins involves using binding competitors to liberate uremic toxins from protein-binding partners. Purpose In this study, we try to identify potential binding competitors that can enhance the dialysis removal of IS and pCS in natural compounds of phytomedicine. Methods We employed microdialysis to evaluate whether Danhong injection (DHI) and its salvianolic acids can increase the free fractions of IS and pCS and thus improve their dialysis efficiency in vitro. Furthermore, we confirmed the positive effects of DHI and salvianolic acids in vivo on chronic kidney disease model rats in which IS and pCS had heavily accumulated. Results DHI significantly increased the dialysis efficiency of IS and pCS by 99.13% and 142.00% in vitro (10-fold dilution), respectively, and by 135.61% and 272.13% in vivo (4.16 ml/kg). Salvianolic acids including lithospermic acid (LA), salvianolic acid A (SaA), tanshinol (DSS), caffeic acid (CA), salvianolic acid B (SaB), protocatechuic aldehyde (PA) and rosmarinic acid (RA) significantly enhanced the dialysis removal of IS and pCS in a concentration-dependent manner. LA, the best competitor of the tested salvianolic acids, increased dialysis efficiency levels of IS and pCS by 197.23% and 198.31% in vitro (400 μM), respectively, and by 119.55% and 127.56% in vivo (24.69 mg/kg). Conclusion The removal of protein-bound uremic toxins IS and pCS using DHI or salvianolic acids as protein-bound competitors is superior to previously reported strategies and drugs and may contribute to clinical hemodialysis therapeutic practice.