Exercise interventions for frail older adults with diabetes: A scoping review.

There is a paucity of evidence on exercise interventions for frail older adults with diabetes. This scoping review aims to identify the scope of the current literature on the characteristics and effects of exercise interventions for frail older adults with diabetes. A search without time limitation was conducted in eight databases. 14 studies were finally included. Resistance exercise and multicomponent exercise were the most common types of exercise. There was considerable variation in the frequency, duration and intensity of exercise interventions. Studies reported improvements in frailty status, physical function, blood glucose and lipid levels and economic effectiveness. The most frequent combined interventions involved nutrition and education. Although evidence was limited, the potential benefits of exercise interventions for frail older adults with diabetes were substantial. Further high-quality studies are needed to explore the most effective and cost-saving exercise interventions for frail older adults with diabetes.

Evaluation of the clinical effect of a multimodal pre-rehabilitation program guided by the behaviour change wheel in elderly women with breast cancer.

BACKGROUND: This study aims to explore the nursing effect of a multimodal pre-rehabilitation programme guided by BCW theory on elderly women patients with breast cancer. METHODS: The participants were divided into two groups. The study group was administered with the pre-rehabilitation model guided by BCW theory; the control group was administered with conventional methods. The rehabilitation effects of the two groups were compared.. RESULTS: The scores of RISC, PTGI and FACT-B were higher in the study group(P < 0.05). The SUPPH score and ROM compliance rate were higher in the study group (P < 0.05) (96% vs 72%). The avoidance score and yield score were lower in the study group(P < 0.05). CONCLUSION: A multimodal pre-rehabilitation program guided by BCW theory can significantly improve the quality of life and functional status of elderly women patients with breast cancer, and its popularisation and application are recommended.

Genetic analysis of seven patients with inherited ichthyosis and Nagashima­type palmoplantar keratoderma.

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole­exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis­like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis­associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.

TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA.

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Halogen-Bond-Promoted Direct Cross-Coupling of Trifluoromethylated Alkyl Bromides with Coumarins/Quinolinones: Unraveling Trifluoromethyl Effects.

This study introduces a novel approach involving XB-mediated cross-coupling of α-trifluoromethylated alkyl bromides with coumarins and quinolinones under visible light irradiation. Both density functional theory (DFT) calculations and experimental studies converge to suggest that the noncovalent interaction between alkyl bromides and DMAP, intensified by the α-trifluoromethyl group, plays a pivotal role in facilitating this chemoselective reaction.

ChatGPT4's Proficiency in Addressing Patients' Questions on Systemic Lupus Erythematosus: A Blinded Comparative Study with Specialists.

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and 5 rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across 6 domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level, and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; p < 0.01) and 0.460 (95% CI, 0.227-0.693 p < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all 6 domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language, and exhibited greater comprehensibility, satisfaction, and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

Recycling Valuable Alkylbenzenes from Polystyrene through Methanol-Assisted Depolymerization.

The vast bulk of polystyrene (PS), a major type of plastic polymers, ends up in landfills, which takes up to thousands of years to decompose in nature. Chemical recycling promises to enable lower-energy pathways and minimal environmental impacts compared with traditional incineration and mechanical recycling. Herein, we demonstrated that methanol as a hydrogen supplier assisted the depolymerization of PS (denoted as PS-MAD) into alkylbenzenes over a heterogeneous catalyst composed of Ru nanoparticles on SiO2. PS-MAD achieved a high yield of liquid products which accounted for 93.2 wt % of virgin PS at 280 °C for 6 h with the production rate of 118.1 mmolcarbon gcatal. -1 h-1. The major components were valuable alkylbenzenes (monocyclic aromatics and diphenyl alkanes), the sum of which occupied 84.3 wt % of liquid products. According to mechanistic studies, methanol decomposition dominates the hydrogen supply during PS-MAD, thereby restraining PS aromatization which generates by-products of fused polycyclic arenes and polyphenylenes.

Dynamic changes of key metabolites in Longjing green tea during processing revealed by widely targeted metabolomic profiling and sensory experiments.

In this study, widely targeted metabolomics and chemometrics were utilized to comprehensively analyse the formation of taste compounds in Longjing green tea. A total of 580 non-volatile metabolites were identified by using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and alterations in three metabolic pathways were investigated. Notably, the fixation process reduced phosphatidic acid levels, resulting in the formation of lyso-phosphatidylcholine and lyso-phosphatidylethanolamine, as well as the release of esterified polyunsaturated fatty acids. Baiye No.1 had high levels of L-glutamic acid and l-glutamine, while Longjing 43 showed elevated levels of flavones. Correlation analysis and sensory verification indicated that the specific concentration of L-leucine could decrease the umami of the tea. These findings advance our understanding of Longjing green tea quality improvement and cultivar development.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Intracytoplasmic Sperm Injection Versus In vitro Fertilization in Infertile Women with Thyroid Autoimmunity.

Background: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared with in vitro fertilization (IVF). Methods: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer (ET) treatment cycle from January 2019 to February 2021. In total, 2171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8702 and 2668 women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy, and live birth after the first ET cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. Results: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in the TAI-positive and IVF group vs. 0.7 [0.5-0.8] in the TAI-positive and ICSI group vs. 0.6 [0.5-0.8] the TAI-negative and IVF group vs. 0.7 [0.5-0.8] in the TAI-negative and ICSI group, p < 0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio [aOR]: 0.80 [confidence interval, CI: 0.67-0.97]; clinical pregnancy: 43.0% vs. 38.8%, aOR: 0.81 [CI: 0.67-0.97]; live birth: 36.2% vs. 32.4%, aOR: 0.81 [CI: 0.66-0.98]). Conclusion: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared with IVF. Further prospective clinical trials are needed to confirm our findings.

Differential effects of oxytetracycline on detoxification and antioxidant defense in the hepatopancreas and intestine of Chinese mitten crab under cadmium stress.

This study aims to evaluate the effects of oxytetracycline (OTC) on detoxification and oxidative defense in the hepatopancreas and intestine of Chinese mitten crab (Eriocheir sinensis) under cadmium (Cd) stress. The crab was exposed to 0.6 µM Cd, 0.6 µM OTC, and 0.6 µM Cd plus 0.6 µM OTC for 42 days. Our results showed that in the intestine, OTC alone enhanced protein carboxylation (PC) and malondialdehyde (MDA) contents, which was associated with the increased OTC accumulation. Compared to Cd alone, Cd plus OTC increased Cd and OTC contents, and reduced detoxification (i.e., glutathione (GSH) content, gene expressions of cytochrome P450 (CYP) isoforms, 7-ethoxyresorufin O-deethylase (EROD) activity, mRNA levels and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), and antioxidant defense (i.e., gene expressions and activities of catalase (CAT) and superoxide dismutase (SOD)) in the intestine, leading to the increased in PC and MDA contents, suggesting that OTC had a synergistic effect on Cd-induced oxidative damage. In the hepatopancreas, although OTC alone increased OTC accumulation, it did not affect PC and MDA contents. Compared to Cd alone, Cd plus OTC reduced MDA content, which was closely related to the improvement of detoxification (i.e., GSH content, mRNA levels of CYP isoforms, EROD activity, gene expressions and activities of GPx, GR and GST), and antioxidant defense (gene expressions and activities of CAT and SOD, metallothionein content). Aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2) transcriptional expressions were positively correlated with most detoxification- and antioxidant-related gene expressions, respectively, indicating that AhR and Nrf2 were involved in the regulation of these gene expressions. Our results unambiguously demonstrated that OTC had tissue-specific effects on Cd-induced toxicological effect in E. sinensis, which contributed to accurately evaluating Cd toxicity modulated by TCs in crab.

A new species and a replacement name in Cynanchum (Apocynaceae, Asclepiadeae) from China.

Cynanchumpingtaoi S.Jin Zeng, G.D.Tang & Miao Liao, sp. nov. (Apocynaceae) from Yunnan Province, China, is described and illustrated based on morphological and molecular evidence. Its deeply cordate to reniform leaves and campanulate, large flowers show that it is a member of former Raphistemma Wall., which has been included in Cynanchum L.. It is different from all former Raphistemma species by the broadly ovate corolla lobes, purple-red corolla and connivent corona tip slightly exceeding the corolla throat. Meanwhile, Cynanchumlonghushanense G.D.Tang & Miao Liao, nom. nov. is proposed as replacement name for Raphistemmabrevipedunculatum Y.Wan, which was considered a synonym of Cynanchumhooperianum (Blume) Liede & Khanum but is here reinstated as a distinct species because of significant morphological differences.

Risk factors for placenta accreta spectrum without prior cesarean section: A case-control study in China.

OBJECTIVE: To identify the risk factors for placenta accreta spectrum (PAS) disorders in women without prior cesarean section (CS). METHODS: This retrospective case-control study investigated patients without prior CS who gave birth at Peking University Third Hospital between January 1, 2015 and December 31, 2021. Patients diagnosed with PAS according to the clinical diagnostic criteria of the 2019 International Federation of Gynecology and Obstetrics (FIGO) classification were included as the study group. Patients were matched as the control group according to delivery date and placenta previa, in a 1:2 allocation ratio. Maternal characteristics were compared between the two groups. RESULTS: The study included 348 patients in the study group and 696 in the control group. The multivariate analysis showed that the independent risk factors of PAS consisted of operative hysteroscopy (once: adjusted odds ratio [aOR] 2.38, 95% CI 1.28-4.24, P = 0.006; twice or more: aOR 5.43, 95% CI 1.04-28.32, P = 0.045), uterine curettage (once: aOR 2.54, 95% CI 1.80-3.58, P < 0.001; twice: aOR 3.01, 95% CI 1.81-5.02, P < 0.001; three or more times: aOR 9.18, 95% CI 4.64-18.18, P < 0.001), multifetal pregnancy (aOR 5.64, 95% CI 3.01-10.57, P < 0.001), adenomyosis (aOR 2.77, 95% CI 1.23-6.22, P = 0.014), in vitro fertilization (aOR 1.51, 95% CI 1.04-2.20, P = 0.030) and pre-eclampsia (aOR 2.72, 95% CI 1.36-5.45, P = 0.005), and the independent protective factor was being multiparous (aOR 0.37, 95% CI 0.25-0.54, P < 0.001). CONCLUSION: After controlling the effect of placenta previa, we found that patients with PAS without prior CS had unique maternal characteristics. Classification and quantification of the intrauterine surgeries they have undergone is essential for identifying high-risk patients. Early identification of high-risk groups by risk factors has the potential to improve the prognosis considerably.

Cough symptoms in children following COVID-19: a single-center retrospective study.

Background: Cough is the most common respiratory symptom in children with mild coronavirus disease 2019 (COVID-19); however, evidence regarding the duration and severity of COVID-19-related cough is sparse. Herein, we investigated the correlation between cough severity/duration and disease duration in children with allergic diseases following COVID-19. Methods: This single-center, retrospective case-control study was conducted at the Department of Pediatrics, Peking University Third Hospital, from February 6-13, 2023. Children aged 0-16 completed a questionnaire survey collecting basic information and weekly cough scores for 8 consecutive weeks after COVID-19 in December 2022. The Kaplan-Meier method was used to draw event curves, and the log-rank method was used to compare inter-group differences. Stepwise regression was applied for multivariate analysis of correlations between age, sex, allergic diseases, and the degree and duration of cough following COVID-19. Results: Overall, 686 children were included, of whom 183 (26.7%) had allergic diseases and 503 (73.3%) did not. Kaplan-Meier analysis identified significant differences between patients with and without allergic disease (log-rank test, P = 0.002) and between patients with no allergic disease and those with one and more than one allergic disease (log-rank test, P = 0.003). Multivariate regression identified a link between the presence of more than one allergic disease and coughing for >4 weeks after infection (P < 0.001). Allergic disease was the primary factor linked to cough symptoms lasting 8 weeks and cough severity (P < 0.001). Conclusions: Allergic disease contributes to the prolonged duration and severity of coughing in children with mild COVID-19.

Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target silencing.

The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, the piRNA pathway and its targeted transposons have coevolved rapidly in a species-specific manner, but how the piRNA pathway adapts specifically to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRNA-induced silencing complexes (piRISCs) bind and cleave targets more efficiently than their invertebrate counterparts from the sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared with EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate-which enforces seed-target fidelity in microRNA RISC-adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mice and humans, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.

EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47.

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

What do they Need?-The academic counseling needs of students majoring in art and design in a higher vocational college in China.

Students in higher vocational education are always encountering various challenges. The way they attempt to conquer these challenges influences their success in achieving their academic goals. With the development of the times, the needs of students in China's vocational colleges to cope with challenges are also changing. In order to understand the changing needs of these students to cope with the challenges, based on Trautwein and Bosse's academic counseling demand model and Knowles's demand theory, this study adopted semi-structured interviews, key event collection methods, and purposive sampling to select 12 students of different grades majoring in art and design in a higher vocational college in Guangzhou, China. With reference to related studies on the key academic needs of students, interview outlines were designed, interviews were conducted, and coding and analysis were performed. Students' experiences were categorized according to learning-related, individual, organization, and social constructs. The study results showed that the academic counseling needs of China's higher vocational art and design students mainly focused on the learning-related construct, such as understanding the courses and course systems they were majoring in, setting and realizing academic goals, coping with setbacks, pressure and other students' comprehensive evaluation. This was followed by dealing with personal and financial issues, building social circles and peer relationships, and so on. Therefore, for students to overcome challenges and achieve academic goals, it is helpful to strengthen the collaboration between professional teachers and counselors, the influence of peers, the focus on academic consulting work related to learning, and to explore and carry out guidance on students' individual needs in higher vocational colleges.