[Interpretation of the UK screening and treatment of retinopathy of prematurity updated 2022 guidelines]. / è‹±å›½æ—©äº§å„¿è§†ç½‘è†œç— å˜çš„ç­›æŸ¥å’Œæ²»ç–—æŒ‡å—2022更新版解读.

The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

The frequency of imaging markers adjusted for time since symptom onset in intracerebral hemorrhage: A novel predictor for hematoma expansion.

BACKGROUND: Hematoma expansion (HE) is common in patients with intracerebral hemorrhage (ICH) and associated with a worse outcome. Imaging makers and shorter time from symptom onset are both associated with HE, but prognostic scores based on these parameters individually have not been satisfactory. We hypothesized that a score including both imaging markers of expansion, and time of onset, would improve prediction. METHODS: Patients with supratentorial ICH within 6 h after onset were consecutively recruited from six centers between January 2018 and August 2022. Three markers were used: hypodensities, the blend sign, and the island sign. We first defined frequency of imaging markers (FIM) as the relationship between the number of imaging markers and onset-to-CT time (OCT). The time-adjusted FIM was defined as the ratio of the number of imaging markers to the onset-to-initial imaging time. Multivariate analysis was performed to determine the relationship between FIM and HE. Receiver operating curve analysis was used to identify potential threshold values of FIM that optimally predict HE. In addition, the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and the area under the curve (AUC) of the optimal cut-off in predicting HE were calculated. RESULTS: In total, 1488 patients were eligible for inclusion, of whom 418 had incident HE. Multivariate analysis showed that age, male sex, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, and FIM were independent predictors of HE (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97-0.99; OR = 1.73, 95% CI = 1.28-2.35; OR = 0.87, 95% CI = 0.83-0.92; OR = 0.42, 95% CI = 0.28-0.62; OR = 7.82, 95% CI = 5.86-10.42, respectively). The optimal cut-off point for FIM in predicting HE was 0.63, with sensitivity, specificity, PPV, NPV, and AUC values of 0.69, 0.89, 0.71, 0.88, and 0.83, respectively. CONCLUSION: The FIM adjusted for time since symptom onset is a significant predictor of HE. Its use may allow improved prediction of those patients with ICH who develop HE, and the score may be clinically applicable in the management of patients with ICH.

Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Cancer cell-autonomous cGAS-STING response confers drug resistance.

The cGAS-STING pathway has long been recognized as playing a crucial role in immune surveillance and tumor suppression. Here, we show that when the pathway is activated in a cancer-cell-autonomous response manner, it confers drug resistance. Targeted or conventional chemotherapy drugs promoted cytosolic DNA accumulation in cancer cells, activating the cGAS-STING pathway and downstream TBK1-IRF3/NF-κB signaling. This cancer cell-intrinsic response enabled the cells to counteract drug stress, allowing treatment resistance to be acquired and maintained. Blockade of stimulator of interferon genes (STING) signaling delayed and overcame resistance in models in vitro and in vivo. This finding uncovers an alternative face of cGAS-STING signaling other than the well-reported modulation of microenvironmental immune cells. It also implies a caution for the combination of STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.

Erratum: Aldehyde dehydrogenase 1A1 confers erlotinib resistance via facilitating the reactive oxygen species-reactive carbonyl species metabolic pathway in lung adenocarcinomas: Erratum.

[This corrects the article DOI: 10.7150/thno.35729.].

A phosphoglycerate mutase 1 allosteric inhibitor overcomes drug resistance to EGFR-targeted therapy via disrupting IL-6/JAK2/STAT3 signaling pathway in lung adenocarcinoma.

Resistance to epidermal growth factor receptor (EGFR) inhibitors, from the first-generation erlotinib to the third generation osimertinib, is a clinical challenge in the treatment of patients with EGFR-mutant lung adenocarcinoma. Our previous work found that a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1), HKB99, restrains erlotinib resistance in lung adenocarcinoma cells. However, the role of HKB99 in osimertinib resistance and its underlying molecular mechanism remains to be elucidated. Herein, we found that IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in both erlotinib and osimertinib resistant cells. Importantly, HKB99 significantly blocks the interaction of PGAM1 with JAK2 and STAT3 via the allosteric sites of PGAM1, which leads to inactivation of JAK2/STAT3 and thereby disrupts IL-6/JAK2/STAT3 signaling pathway. Consequently, HKB99 remarkably restores EGFR inhibitor sensitivity and exerts synergistic tumoricidal effect. Additionally, HKB99 alone or in combination with osimertinib down-regulated the level of p-STAT3 in xenograft tumor models. Collectively, this study identifies PGAM1 as a key regulator in IL-6/JAK2/STAT3 axis in the development of resistance to EGFR inhibitors, which could serve as a therapeutic target in lung adenocarcinoma with acquired resistance to EGFR inhibitors.

The prognosis of patients with extremity osteosarcoma who have undergone misdiagnosis and mistreatment / 中华骨科杂志

Objective:To compare outcomes between standardized and misdiagnosis and mistreatment of osteosarcoma.Methods:A retrospective analysis of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (299 cases, control group) and those who were misdiagnosed (benign or infective) and received mistreatment (23 cases, study group) between January 2009 and December 2021. Gender, age, first operation mode, recurrence time, recurrence interval, metastasis time, metastasis interval, total survival time (months), survival status in the two group and tumor site reoperation mode in the study group were statistically analyzed. Further, chi-square test was performed for comparison of the clinical between two groups. The survival analysis was performed using Kaplan-Meier test and Log-rank test.Results:All the 322 patients were followed up. In the control group, the average follow-up time was 42 months (1-137 months), the average age was 24 years (3-80 years), male 184 cases, female 115 cases, and limb salvage rate was 85.3% (255/299). Seven patients underwent amputation, and the amputation rate was 17.7% (44/299). The recurrence rate was 8.4% (25/299), the average recurrence interval was 22.8 months (7-36 months), and the metastasis rate was 28.1% (85/299), the average metastasis time was 32.7 months (0-58 months). In the study group, the average of follow-up time was 30 months (9-117 months), the average age was 36 years (5-67 years), 17 males and 6 females. Among them, eleven patients were treated with limb salvage in the second stage, and the limb salvage rate was 47.8% (11/23). Seven patients underwent amputation, and the amputation rate was 30.4% (7/23). The recurrence rate was 26.1% (6/23), the average recurrence interval was 11 months (1-42 months), and the metastasis rate was 43.4% (10/23), the average metastasis time was 20.3 months (1-44 months). The 5-year survival rate was 50.7% in the study group and 56.1% in the control group. There was no significant difference between the two groups (χ 2=0.09, P=0.760). Conclusion:The overall prognosis of patients with high-grade osteosarcoma who receive active treatment after mistreatment is similar to that of patients with standardized treatment, but the recurrence and metastasis rate is higher, the recurrence time is earlier, and the amputation rate is higher.

A detailed assessment of liver function in patients with hepatocellular carcinoma via the modified albumin-bilirubin (mALBI) grade.

Recently, the albumin-bilirubin (ALBI) score, a continuous index consisting of only albumin and bilirubin, has been developed for objectively assessing liver function in patients with hepatocellular carcinoma (HCC). However, the ALBI score was arbitrarily categorized into three ALBI grades based on two artificially predetermined cutoff points with no explanation and statistical grounds, causing a considerable loss of discriminatory ability. This study aims to propose a modified ALBI (mALBI) grade for offering a detailed evaluation of hepatic reserve and specify its role during clinical practice in the HCC setting. The study population comprised 3540 HCC patients treated with mainstream therapies including hepatectomy (n=2056), thermal ablation (n=550), and transcatheter arterial chemoembolization (n=934) from 2002 to 2017. The ALBI score was stratified into four mALBI grades through a recently proposed statistical method aiming to select the optimal cutoff points of a continuous predictive variable by maximizing the discriminative ability in a multivariable Cox regression model. The mALBI grade had an overall better discriminatory ability than the ALBI grade in predicting overall survival through Harrell's C-index (0.614 vs. 0.598, P<0.001). Both visual inspections of Kaplan-Meier curves and calculation of hazard ratios displayed a more subtle evaluation of liver function using the mALBI grade. Moreover, the newly identified cut-point (ALBI score = -2.29) between the mALBI grade 2a and 2b was much closer to a 30% retention rate of indocyanine green at 15 minutes, an indicator for the performance of a subsegmentectomy. The newly proposed mALBI grade provides a more subtle assessment of liver function to guide clinical decision-making and predicts the prognosis of HCC patients more accurately than the original ALBI grade.

Comparative Transcriptome Sequencing Analysis of Hirudo nipponia in Different Growth Periods.

Hirudo nipponia is the only blood-sucking leech included in Chinese Pharmacopoeia having distinct features of anticoagulation, exorcizing blood stasis, and promoting menstruation. Despite such significant characteristics, very little is known about its molecular genetics and related physiological mechanisms. In this study, the transcriptomes of H. nipponia at three developmental stages (larvae, young, and adults), revealed a total of 1,348 differentially expressed genes (DEGs), 223 differentially expressed lncRNAs, and 88 novel mRNAs. A significant diverse gene expression patterns were observed at different developmental stages which were analyzed by differential gene expression trends, and the overall gene expression trends consist of three overall down-regulated trends, and two overall up-regulated trends. Furthermore, the GO and KEGG enrichment functional annotation analysis revealed that these DEGs were mainly associated with protein hydrolysis, signal transduction, energy metabolism, and lipid metabolism while growth, development, metabolism, and reproduction-related DEGs were also found. Additionally, real-time quantitative PCR results confirmed deep sequencing results based on the relative expression levels of nine randomly selected genes. This is the first transcriptome-based comprehensive study of H. irudo nipponia at different developmental stages which provided considerable deep understanding related to gene expression patterns and their relevant developmental pathways, neurodevelopmental and reproductive characteristics of the leech.

Surgical management of sacral neurogenic tumors / 中国骨伤

OBJECTIVE@#To observe the efficacy and complications of one-stage tumor resection to treat primary sacral neurogenic tumors and to discuss some details in the clinically relevant anatomy.@*METHODS@#A retrospective analysis of 26 patients with neurogenic turors of the sacral spine who were surgically treated from January 2001 to January 2018, including 16 males and 10 females, aged from 21 to 69 years old with an average age of (39.3±10.9) years old. The courses of diseases ranged from 3 to 56 months with an average of (17.9±10.1) months. The diameters of presacral components ranged from 3.3 to 19.6 cm with an average of (8.7±4.1) cm. The proximal margin of presacral lesions was above the L5S1 level in 6 cases, and lower than L5S1 in 20 cases. A posterior incision approach for one-stage complete resection of the tumor was used firstly, and an anterior approach was combined when necessary. Spinal-pelvic reconstruction with the modified Galveston technique was also carried out in relevant cases. Whether to preserve the tumor-involved nerve roots depended on the situation during the operation. The operation time, intraoperative blood loss, pain relief, and complications were recorded. The lumbosacral spine stability and sacral plexus neurological function were evaluated during postoperative follow-up, and local recurrence and distant metastasis were examined as well.@*RESULTS@#Total excision was achieved in all 26 patients, with an operation time of (160.4±35.3) mins and an intraoperative blood loss of (1 092.3±568.8) ml. Tumors have been removed via a posterior-only approach in 21 cases and via combined anterior/posterior approaches in 5 cases. The diameter of presacral masses components ranged from 11.3 to 19.6 cm with an average of (15.1±3.2) cm in patients with combined anterior/posterior approaches, and ranged from 3.3 to 10.9 cm with an average of (7.2±2.4) cm in patients with a posterior-only approach. Five of the six patients whose proximal margin of presacral masses was above the L5S1 level adopted combined anterior/posterior approaches, and 20 patients lower than the L5S1 level adopted the posterior-only approach. All the patients were followed up for 6 to 82 months with an average of(45.4±18.2)months. Postoperative lumbosacral pain and lower extremity radicular pain were significantly relieved, and sensation, muscle strength and bowel and bladder function were also improved to varying degrees. The postoperative early complications included superficial wound infection in 1 case and cerebrospinal fluid leakage in 2 cases. Pathology confirmed 17 cases of schwannoma, 7 cases of neurofibroma and 2 cases of malignant schwannoma. Local recurrence was observed in two cases of benign neurogenic tumors. One patient with a malignant nerve sheath tumor had lung metastasis, who died 20 months after the operation. In 17 cases of upper sacral neurogenic tumors, 4 cases did not undergo spinal-pelvic reconstruction with internal fixation, of which 2 cases suffered from postoperative segmental instability. Tumor-involved nerve roots were resected during surgery in 7 cases. One of these patients who had S2 and S3 nerve roots sacrificed simultaneously had an impaired bladder and bowel function postoperatively, and did not recover completely. In the other 6 cases, the neurological function was not damaged obviously or recovered well.@*CONCLUSION@#The posterior approach can directly expose the lesions, and it is also convenient to deal with nerve roots and blood vessels. The operation time, intraoperative blood loss, degree of symptom relief, complication rate, and recurrence and metastasis rate can be controlled at an appropriate level. It is a safe and effective surgical approach. When the upper edge of the presacral mass is higher than the L5S1 level or the diameter of the presacral mass exceeds 10 cm, an additional anterior approach should be considered. The stress between the spine and pelvis is high, and internal fixation should be used to restore the mechanical continuity of the spine and pelvis during resection of neurogenic tumors of the high sacral spine. Most of the parent nerve roots have lost their function. Resection of a single parent nerve root is unlikely to cause severe neurological dysfunction, while the adjacent nerve roots have compensatory functions and should be preserved as much as possible during surgery.

Targeting AKR1B1 inhibits glutathione de novo synthesis to overcome acquired resistance to EGFR-targeted therapy in lung cancer.

Acquired resistance represents a bottleneck to molecularly targeted therapies such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. A deeper understanding of resistance mechanisms can provide insights into this phenomenon and help to develop additional therapeutic strategies to overcome or delay resistance. Here, we identified a pharmacologically targetable metabolic mechanism that drives resistance to EGFR TKIs in lung cancer cell lines and patient-derived xenograft mice. We demonstrated that aldo-keto reductase family 1 member B1 (AKR1B1) interacts with and activates signal transducer and activator of transcription 3 (STAT3) to up-regulate the cystine transporter solute carrier family 7 member 11 (SLC7A11). This leads to enhanced cystine uptake and flux to glutathione de novo synthesis, reactive oxygen species (ROS) scavenging, protection from cell death, and EGFR TKI drug resistance in lung cancer cell lines and xenograft mouse models. Suppression of AKR1B1 with selective inhibitors, including the clinically approved antidiabetic drug epalrestat, restored the sensitivity of resistant cell lines to EGFR TKIs and delayed resistance in lung cancer patient-derived xenograft mice. Our findings suggest a metabolic mechanism for resistance to a molecularly targeted therapy and provide a potential therapeutic target for overcoming resistance to EGFR TKIs, including the third-generation inhibitor osimertinib.

Primary cystic and solid neuroendocrine tumor of the retroperitoneum: A case report.

RATIONALE: Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs. PATIENT CONCERNS: A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup. DIAGNOSES: The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery. INTERVENTIONS: The patient underwent resection of the large retroperitoneal tumor. OUTCOMES: The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment. LESSONS SUBSECTIONS: When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.

NRF2-GPX4/SOD2 axis imparts resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer cells.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved satisfactory clinical effects in the therapy of non-small cell lung cancer (NSCLC), but acquired resistance limits their clinical application. NRF2 has been shown to enhance the resistance to apoptosis induced by radiotherapy and some chemotherapy. In this study, we investigated the role of NRF2 in resistance to EGFR-TKIs. We showed that NRF2 protein levels were markedly increased in a panel of EGFR-TKI-resistant NSCLC cell lines due to slow degradation of NRF2 protein. NRF2 knockdown overcame the resistance to EGFR-TKIs in HCC827ER and HCC827GR cells. Furthermore, we demonstrated that NRF2 imparted EGFR-TKIs resistance in HCC827 cells via upregulation of GPX4 and SOD2, and suppression of GPX4 and SOD2 reversed resistance to EGFR-TKIs. Thus, we conclude that targeting NRF2-GPX4/SOD2 pathway is a potential strategy for overcoming resistance to EGFR-TKIs.

ColorCells: a database of expression, classification and functions of lncRNAs in single cells.

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.