Programmed cell death disrupts inflammatory tumor microenvironment (TME) and promotes glioblastoma evolution.

Glioblastoma (GBM) is the most common malignant brain tumor and has a dismal prognosis even under the current first-line treatment, with a 5-year survival rate less than 7%. Therefore, it is important to understand the mechanism of treatment resistance and develop new anti-tumor strategies. Induction of programmed cell death (PCD) has become a promising anti-tumor strategy, but its effectiveness in treating GBM remains controversial. On the one hand, PCD triggers tumor cell death and then release mediators to draw in immune cells, creating a pro-inflammatory tumor microenvironment (TME). One the other hand, mounting evidence suggests that PCD and inflammatory TME will force tumor cells to evolve under survival stress, leading to tumor recurrence. The purpose of this review is to summarize the role of PCD and inflammatory TME in the tumor evolution of GBM and promising methods to overcome tumor evolution.

Atomic order of rare earth ions in a complex oxide: a path to magnetotaxial anisotropy.

Complex oxides offer rich magnetic and electronic behavior intimately tied to the composition and arrangement of cations within the structure. Rare earth iron garnet films exhibit an anisotropy along the growth direction which has long been theorized to originate from the ordering of different cations on the same crystallographic site. Here, we directly demonstrate the three-dimensional ordering of rare earth ions in pulsed laser deposited (EuxTm1-x)3Fe5O12 garnet thin films using both atomically-resolved elemental mapping to visualize cation ordering and X-ray diffraction to detect the resulting order superlattice reflection. We quantify the resulting ordering-induced 'magnetotaxial' anisotropy as a function of Eu:Tm ratio using transport measurements, showing an overwhelmingly dominant contribution from magnetotaxial anisotropy that reaches 30 kJ m-3 for garnets with x = 0.5. Control of cation ordering on inequivalent sites provides a strategy to control matter on the atomic level and to engineer the magnetic properties of complex oxides.

Heterogeneous integration of spin-photon interfaces with a CMOS platform.

Colour centres in diamond have emerged as a leading solid-state platform for advancing quantum technologies, satisfying the DiVincenzo criteria1 and recently achieving quantum advantage in secret key distribution2. Blueprint studies3-5 indicate that general-purpose quantum computing using local quantum communication networks will require millions of physical qubits to encode thousands of logical qubits, presenting an open scalability challenge. Here we introduce a modular quantum system-on-chip (QSoC) architecture that integrates thousands of individually addressable tin-vacancy spin qubits in two-dimensional arrays of quantum microchiplets into an application-specific integrated circuit designed for cryogenic control. We demonstrate crucial fabrication steps and architectural subcomponents, including QSoC transfer by means of a 'lock-and-release' method for large-scale heterogeneous integration, high-throughput spin-qubit calibration and spectral tuning, and efficient spin state preparation and measurement. This QSoC architecture supports full connectivity for quantum memory arrays by spectral tuning across spin-photon frequency channels. Design studies building on these measurements indicate further scaling potential by means of increased qubit density, larger QSoC active regions and optical networking across QSoC modules.

Comparative long-term outcomes of airway resection and functional reconstruction for papillary thyroid cancer.

INTRODUCTION: The surgical management of patients diagnosed with papillary thyroid carcinoma (PTC) and tracheal invasion has been a subject of ongoing discussion, particularly regarding the approach to tracheal functional reconstruction. The objective of this study was to examine the surgical technique and prognosis of PTC patients with tracheal invasion. MATERIALS AND METHODS: This study employed both univariate and multivariate Cox proportional hazard models to determine predictive factors that affect the progression-free survival (PFS) of PTC patients with tracheal invasion. Cox regression analysis was conducted by using R software version 4.3.1. RESULTS: In our study, we included 247 patients with T4a PTC. Among them, 146 patients (59.1 %) were classified as Shin I, 57 patients (23.1 %) as Shin II-III, and 44 patients (17.8 %) as Shin IV. Patients in the Shin I group underwent shaving of the tumours in the airway. The preferred surgical methods in the Shin II, III and IV groups were window resection (66.7 %), sleeve resection (34.8 %) and partial tracheal resection and skin fistula (61.8 %), respectively. Multivariate analysis demonstrated that neither tracheal surgery nor reconstruction procedures had an impact on PFS in T4a PTC patients with tracheal invasion. The 5-year DSS rate for patients receiving radioiodine (RAI) therapy was 87.3 % (p = 0.033). CONCLUSION: This study confirmed that tracheal surgery and reconstruction methods had no impact on PFS in T4a PTC patients with tracheal invasion in different Shin groups. Furthermore, RAI therapy has the potential to increase the survival rate of patients with preoperative distant metastasis of T4a PTC.

Oxidative potential associated with reactive oxygen species of size-resolved particles: The important role of the specific sources.

Oxidative potential (OP) is a predictor of particulate matter (PM) toxicity. Size-resolved PM and its components that influence OP values can be generated from several sources. However, There is little research have attempted to determine the PM toxicity generated from specific sources. This paper studied the OP characterization and reactive oxygen species (ROS) formation of particles from specific sources and their effects on human health. OP associated with ROS of size-resolved particles was analyzed by using dithiothreitol (DTT) method and electron paramagnetic resonance (EPR) spectroscopy technology. And OP and ROS deposition of specific source PM were calculated for health through the Multi-path particle deposition (MPPD) model. The results evidenced that the highest water-soluble OP (OPws) from traffic sources (OPm: 104.50 nmol min-1·ug-1; OPv: 160.15 nmol min-1·m-3) and the lowest from ocean sources (OPm: 22.25 nmol⋅min-1⋅ug-1; OPv: 54.16 nmol min-1·m-3). The OPws allocation in PM from different sources all have a unimodal pattern range from 0.4 to 3.2 µm. ROS (·OH) displayed the uniform trend as PM OPws, indicating that PM< 3.2 is the major contributor to adverse health impacts for size-resolved PM because of its enhanced oxidative activity compared with PM> 3.2. Furthermore, this study predicted the DTT consumption of PM were assigned to different components. Most DTT losses are attributed to the transition metals. For specific sources, transition metals dominates DTT losses, accounting for 38%-80% of DTT losses from different sources, followed by Hulis-C, accounting for 1%-10%. MPPD model calculates that over 66% of pulmonary DTT loss comes by PM< 3.2, and over 71% of pulmonary ROS generation from PM< 3.2. Among these sources of pollution, traffic emissions are the primary contributors to reactive oxygen species (ROS) in environmental particulate matter (PM). Therefore, emphasis should be placed on controlling traffic emissions, especially in coastal areas.

Concentration properties of biopolymers via dead-end forward osmosis.

Extracellular polymeric substances (EPSs) in excess sludge of wastewater treatment plants are valuable biopolymers that can act as recovery materials. However, effectively concentrating EPSs consumes a significant amount of energy. This study employed novel energy-saving pressure-free dead-end forward osmosis (DEFO) technology to concentrate various biopolymers, including EPSs and model biopolymers [sodium alginate (SA), bovine serum albumin (BSA), and a mixture of both (denoted as BSA-SA)]. The feasibility of the DEFO technology was proven and the largest concentration ratios for these biopolymers were 94.8 % for EPSs, 97.1 % for SA, 97.8 % for BSA, and 98.4 % for BSA-SA solutions. An evaluation model was proposed, incorporating the FO membrane's water permeability coefficient and the concentrated substances' osmotic resistance, to describe biopolymers' concentration properties. Irrespective of biopolymer type, the water permeability coefficient decreased with increasing osmotic pressure, remained constant with increasing feed solution (FS) concentration, increased with increasing crossing velocity in the draw side, and showed little dependence on draw salt type. In the EPS DEFO concentration process, osmotic resistance was minimally impacted by osmotic pressure, FS concentration, and crossing velocity, and monovalent metal salts were proposed as draw solutes. The interaction between reverse diffusion metal cations and EPSs affected the structure of the concentrated substances on the FO membrane, thus changing the osmotic resistance in the DEFO process. These findings offer insights into the efficient concentration of biopolymers using DEFO.

Female university students' fertility intentions and their psychosocial factors.

BACKGROUND: Raising the birth rate can effectively increase the resulting labour supply and minimise the adverse impact of an ageing population on high-quality economic development since the demographic dividend is rapidly declining. The Chinese government has a "three-child" policy in place, yet the fertility rate is still falling. This study intends to investigate the present fertility intentions of female university students and assess the extent to which feminism has affected their intentions. It will next investigate the degree to which and the mechanisms by which the psychosocial factors have an impact on those intentions. METHODS: A cross-sectional survey of female university students was conducted in Nanjing, China, from February to March 2023. To assure the representativeness of the sample, a technique of stratified proportional sampling, PPS sampling, and convenience sampling was utilized. A total of 1124 valid samples were acquired from female university students in 15 comprehensive universities. The data were mined and analysed by SPSS (version 24.0) and AMOS (version 24.0) software. RESULTS: Overall female university students' fertility intentions are low at this stage, with more than half (53.55%) of them having no clear desire to have children. The level of feminist identity significantly negatively affected the Intensity of desire to have children (-0.32) and child-number desires (-0.7). Psychosocial factors had a greater degree of influence on fertility intentions. The direct effect of the level of feminist identity and the perception of fertility hindrances on childbearing desires was -0.63 and -0.50 respectively, and the direct effect of the perception of fertility supports on childbearing intentions was 0.79. CONCLUSION: The level of feminist identity is significantly and negatively related to childbearing desires. Psychosocial factors have a greater degree of influence on fertility intentions, with the level of feminist identity, the perception of fertility hindrances and the perception of fertility supports all significantly impacting fertility intentions. The findings of this study emphasise the importance of the government providing a full range of social security and employers providing better employee benefits to promote a fertility-friendly society.

Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies.

Indole is a prestigious heterocyclic skeleton widely found in both naturally-occurring and biologically-active compounds. Pharmaceutical agents containing an indole skeleton in their framework possess a wide range of pharmacological properties, including antiviral, antitumor, analgesic, and other therapeutic activities, and many indole-containing drugs have been proven to have excellent pharmacokinetic and pharmacological effects. Over the past few decades, the FDA has approved over 40 indole-containing drugs for the treatment of various clinical conditions, and the development of indole-related drugs has attracted significant attention from medicinal chemists. This review aims to provide an overview of all the approved drugs that contain an indole nucleus, focusing on their targets, pharmacological activities, and SAR studies.

Validation of the Chinese version of the diabetes health profile to predict the impact of mobile health education on quality of life in type 2 diabetes patients.

Purpose: The Diabetes Health Profile (DHP18), initially created in the United Kingdom, currently lacks a Chinese version. This study endeavors to authenticate the Chinese adaptation of the DHP18 and assess the influence of mobile health (mHealth) education intervention on the quality of life of individuals living with diabetes. Patients and methods: The study included 470 Type 2 diabetes Mellitus (T2DM) patients (204 men, 266 women), spanning an age range of 19-79 years, with an average age of 54 ± 12.40 years. Data analysis employed Jamovie and Mplus software. Moreover, test-retest reliability was evaluated in 52 hospitalized T2DM patients through two repeated measurements taken 4 weeks apart. Results: The Chinese version DHP18 scale exhibited high reliability, evidenced by a Cronbach's alpha of 0.88, and coefficient of test-retest reliability of 0.84. Individual subscales also demonstrated strong reliability, ranging from 0.76 to 0.84, with test-retest reliability spanning from 0.71 to 0.74. Confirmatory Factor Analysis (CFA) employing a three-factor structure (χ2 = 294.69, GFI = 0.92, TLI = 0.91, RMSEA = 0.05, SRMR = 0.06) validated the scale's construct validity. Notably, there was a statistically significant difference (p < 0.05) in the quality of life between Type 2 diabetes patients using mHealth education intervention and those without mHealth education intervention. Mediation analysis revealed that Appraisal of Diabetes (ADS) and Self-Management Efficacy (SED) mediated the effects of Psychological Distress (PD) and Behavior Adherence (BA) on quality of life, both significant direct and indirect effects (p < 0.001). In addition, Dietary Abstinence (DE) displayed significant overall impact (ß = -0.13, p < 0.001) and indirect influence (ß = -0.10, p < 0.01) on diabetic patients' quality of life, though lacking a significant direct effect (ß = -0.03, p = 0.38). Conclusion: The Chinese version of the Diabetes Health Profile Scale meets stringent psychometric standards and stands as an appropriate measurement tool for Chinese T2DM patients, maintaining comparable results to the original scale's structure. The mHealth education intervention yielded a notably positive impact on the quality of life among T2DM patients. Mediation analysis revealed that the three dimensions of the DHP were mediated by Appraisal of Diabetes and Diabetes Self-Management Efficacy, partially mediated by Psychological Distress and Behavior Adherence, and fully mediated by Dietary Abstinence, providing insight into the positive effects of the mHealth model on the quality of life of diabetic patients.

Reinforcement Learning-Guided Long-Timescale Simulation of Hydrogen Transport in Metals.

Diffusion in alloys is an important class of atomic processes. However, atomistic simulations of diffusion in chemically complex solids are confronted with the timescale problem: the accessible simulation time is usually far shorter than that of experimental interest. In this work, long-timescale simulation methods are developed using reinforcement learning (RL) that extends simulation capability to match the duration of experimental interest. Two special limits, RL transition kinetics simulator (TKS) and RL low-energy states sampler (LSS), are implemented and explained in detail, while the meaning of general RL are also discussed. As a testbed, hydrogen diffusivity is computed using RL TKS in pure metals and a medium entropy alloy, CrCoNi, and compared with experiments. The algorithm can produce counter-intuitive hydrogen-vacancy cooperative motion. We also demonstrate that RL LSS can accelerate the sampling of low-energy configurations compared to the Metropolis-Hastings algorithm, using hydrogen migration to copper (111) surface as an example.

Impact of lateral cervical lymph node metastasis on lung metastasis in pediatric thyroid cancer: A correlation study.

BACKGROUND: Thyroid cancer (TC) frequently manifests with lung metastases in the pediatric population, occurring at a significant rate of 30 %. This study aims to evaluate the impact of regional patterns of cervical lymph node metastases on lung metastases in pediatric TC. METHODS: Retrospective analysis was conducted on data from pediatric TC patients spanning the years 2000 to 2018. We compared the rates of lymph node metastasis (LNR), the number of lymph node metastases, and the number of dissected lymph nodes in the central and lateral cervical regions between patients with and without lung metastases. Statistical methods were employed to adjust for confounders during hypothesis testing. RESULTS: A total of 227 pediatric patients, with a median age of 15.12 ± 2.84 years, were included in the study. Of these, 202 (89 %) exhibited LN metastasis, with 40(17.62 %) patients presenting with lung metastasis. Patients with lung metastases were found to be younger (13.40 ± 3.11 vs. 15.50 ± 2.64, p < 0.001), had larger primary tumor diameters (3.49 ± 1.98 vs. 2.31 ± 1.45, p < 0.001), and exhibited a higher number of lymph node metastases (23.40 ± 10.75 vs. 14.65 ± 13.16, p < 0.001). Notably, in patients with LN metastases, the presence of >12 lateral cervical lymph node metastases emerged as a significant risk factor for lung metastases. Among children with metachronous lung metastases, the median time to detection of lung metastases was 43 (12-132) months, and they appeared to receive a greater proportion of radioactive iodine (RAI) treatment compared to those with synchronous lung metastases. CONCLUSION: Lateral cervical lymph node metastasis independently predicts the likelihood of lung metastases in pediatric TC. Furthermore, our findings emphasize the importance of thorough examination of the lungs during follow-up, particularly when the number of metastatic lateral cervical lymph nodes exceeds 12.

The role of targeted therapy and/or immunotherapy therapy in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly invasive malignant tumor with a poor prognosis. Traditional treatment methods have not been effective. However, advancements in targeted therapy and immunotherapy in recent years have shed new light on the management of ATC. The aim of this study was to examine the treatment plan and prognostic factors of ATC. METHODS: This study conducted a retrospective analysis of ATC patients who received treatment at our institution between 2000 and 2023 to evaluate the clinical characteristics, treatment methods, and factors influencing survival. Survival analysis was performed by the Kaplan‒Meier method and log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The 6-month and 1-year disease-specific OS rates were 49% and 29%, respectively. The presence of clinical symptoms and the timing of treatment significantly impacted patient prognosis (P < 0.05). Compared with surgery + radiotherapy/chemotherapy and only surgery, targeted therapy and targeted + immunotherapy represented an improved overall survival, The 6-month/1-year survival rates of which were 81%/61% and 91%/73% (P < 0.05), respectively. Multivariate analysis indicated that the symptoms at initial diagnosis, year of presentation, performance status and treatment plan were independent factors affecting the prognosis. The year of presentation (P = 0.048) and the treatment plan (P = 0.038) were significantly meaningful in predicting prognosis. CONCLUSION: Targeted therapy and targeted+immune therapy can effectively prolong the survival period of ATC patients. Symptoms at initial diagnosis and treatment plan have a significant impact on the prognosis.

Prognostic Significance of Primary Tumor Surgery in Adenoid Cystic Carcinoma Patients With Distant Metastases at Diagnosis: A Population-Based Database Analysis in Head and Neck Region.

Purpose: Adenoid cystic carcinoma (ACC) is an aggressive cancer that often leads to poor prognosis, especially when it has metastasized. The prognostic significance of primary tumor surgery (PTS) for ACC with distant metastasis (DM) at the time of diagnosis has not been extensively studied. Methods: Using data from the surveillance, epidemiology, and end results (SEER) database from 2010 to 2019, we identified patients with ACC in head and neck region and synchronous DM. We evaluated the effect of PTS on different patterns of metastasis using Kaplan-Meier analysis, log-rank tests, and multivariate Cox regression analysis to assess the therapeutic benefit of PTS in the overall cohort and various subgroups. Results: Of the 192 identified patients with synchronous metastatic ACC of head and neck, 91 (47.4%) underwent PTS. Patients who received PTS had significantly better survival than nonsurgical patients (median overall survival: 19 vs 43 months, P = .006). Cox regression analysis also showed that PTS was associated with improved survival (HR = .46, 95% CI: 0.42-0.88; P = .028). In sub-analyses, except for patients with liver metastases [overall survival (OS), P = .107, cancer-specific survival (CSS), P = .153], PTS consistently conferred significant survival benefits in patients with bone metastases (OS, P = .041, CSS, P = .065) and lung metastases (OS, P = .016, CSS, P = .027). PTS also led to better survival in patients who did not receive radiotherapy (median OS: 13 vs 52 months, P = .007). Conclusion: Our study suggests that PTS in metastatic ACC patients of head and neck improved overall and CSS, particularly in those with bone or lung metastases and those who did not receive radiotherapy. However, further prospective studies are needed to confirm these findings, and the indications for PTS in metastatic ACC should be carefully evaluated by a multidisciplinary board.

Kruppel-like factor 13 acts as a tumor suppressor in thyroid carcinoma by downregulating IFIT1.

BACKGROUND: Kruppel-like factor 13 (KLF13) is a transcription factor and plays an important role in carcinogenesis. However, the significance of KLF13 in thyroid carcinoma (THCA) is underdetermined. In this study, we aimed to explore the clinical relevance and function of KLF13 in the progress of THCA. METHODS: The expression of KLF13 in thyroid carcinoma and normal tissue was investigated by qPCR and IHC assay. The expression of KLF13 and IFIT1 in cell samples was investigated with Western blot assay. Cell proliferation ability was detected with CCK8 and colony formation assay. Cell growth in vivo with or without KLF13 overexpression was evaluated on a xenograft model. Cell migration ability was measured with Transwell assay. Cell cycle was detected with flow cytometer. The downstream genes of KLF13 were screened using RNA-seq assay. Luciferase activity was employed to assess the transcriptional regulation of KLF13 on IFIT1 promoter. RESULTS: KLF13 expression was downregulated in THCA samples. KLF13 knockdown and overexpression promoted and inhibited the proliferation and migration of THCA cells, respectively. The RNA-seq, RT-qPCR and immunoblotting data showed that KLF13 knockdown significantly potentiated IFIT1 expression at both mRNA and protein levels. Luciferase assays showed that KLF13 suppressed the transcription activity of IFIT1 promoter. Besides, IFIT1 upregulation was critical for the proliferation and migration of THCA cell lines. Lastly, silencing of IFIT1 greatly reversed the proliferation and migration induced by KLF13 knockdown. CONCLUSIONS: In conclusion, KLF13 may function as an anti-tumor protein in THCA by regulating the expression of IFIT1 and offer a theoretical foundation for treating thyroid carcinoma.

The role of multifocality in predicting central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma.

Objective: To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Study design: Retrospective review. Setting: Tertiary medical center. Methods: We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. Results: (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). Conclusion: In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions.

Interplay between TRIM7 and antiviral immunity.

TRIM7 has been demonstrated to have significant roles in promoting host defense against viral infections and regulating immune signaling pathways. As an E3 ubiquitin ligase, it catalyzes the ubiquitination of various substrates, including adaptor proteins (MAVS and STING) and transcription factors (NF-κB and IRF3), thereby exerting positive or negative regulation on immune signal pathways. However, viruses have developed immune evasion mechanisms to counteract TRIM7. Some viruses can inhibit TRIM7 function by targeting it for degradation or sequestering it away from its targets. Moreover, TRIM7 may even facilitate viral infection by ubiquitinating viral proteins, including envelope proteins that are critical for tissue and species tropism. A comprehensive understanding of the interaction between TRIM7 and antiviral immunity is crucial for the development of innovative treatments for viral diseases.

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain cancer in adults. It is always resistant to existing treatments, including surgical resection, postoperative radiotherapy, and chemotherapy, which leads to a dismal prognosis and a high relapse rate. Therefore, novel curative therapies are urgently needed for GBM. Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved life expectancy for hematological malignancies patients, and thus it increases the interest in applying CAR-T cell therapy for solid tumors. In the recently published research, it is indicated that there are numerous obstacles to achieve clinical benefits for solid tumors, especially for GBM, because of GBM anatomical characteristics (the blood-brain barrier and suppressive tumor microenvironment) and the tumor heterogeneity. CAR-T cells are difficult to penetrate blood-brain barrier, and immunosuppressive tumor microenvironment (TME), which induces CAR-T cell exhaustion, impairs CAR-T cell therapy response. Moreover, under the pressure of CAR-T cell therapy, the tumor heterogeneity and tumor plasticity drive tumor evolution and therapy resistance, such as antigen escape. Nonetheless, scientists strive for strategies to overcome these hurdles, including novel CAR-T cell designs and regional delivery. For instance, the structure of multi-antigen-targeted CAR-T cells can enrich CAR-T accumulation in tumor TME and eliminate abundant tumor cells to avoid tumor antigen heterogeneity. Additionally, paired with an immune modifier and one or more stimulating domains, different generation of innovations in the structure and manufacturing of CAR-T cells have improved efficacy and persistence. While single CAR-T cell therapy receives limited clinical survival benefit. Compared with single CAR-T cell therapy, the combination therapies have supplemented the treatment paradigm. Combinatorial treatment methods consolidate the CAR-T cells efficacy by regulating the tumor microenvironment, optimizing the CAR structure, targeting the CAR-T cells to the tumor cells, reversing the tumor-immune escape mechanisms, and represent a promising avenue against GBM, based on multiple impressive research. Moreover, exciting results are also reported to be realized through combining effective therapies with CAR-T cells in preclinical and clinical trials samples, have aroused inspiration to explore the antitumor function of combination therapies. In summary, this study aims to summarize the limitation of CAR-T cell therapies and introduces novel strategies to enhance CAR-T cell function as well as prospect the potential of the therapeutic combination.

Risk factors for poor progression of addictive internet use across different COVID-19 periods in China.

BACKGROUND AND OBJECTIVES: Addictive behaviors are serious factors for mental health and usually increase during public crises. We identified the vulnerable characteristics for bad prognosis of addictive internet use across different periods of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Self-reported questionnaires were delivered in three waves through jdh.com during the outbreak (n = 17,960), remission (n = 15,666), and dynamic zero (n = 12,158) periods of COVID-19 pandemic in China. Internet addiction degree was assessed using the Internet Addiction Test. The different progression groups were divided using a latent class growth model among 1679 longitudinal participants. Risk factors for bad progression were identified by two-step logistic regression. RESULTS: A total of 40.16% of participants reported an increase in the addictive degree of internet use compared with prepandemic. Across different COVID-19 periods, the overall trend of addictive internet use was downward among general Chinese study participants (Mslope = -1.56). Childhood traumatic experiences, deterioration of physical health, depression, and anxiety during remission and dynamic periods were the main risk factors for the bad progression of pandemic-induced addictive internet use. DISCUSSION AND CONCLUSIONS: Addictive internet use was remitted following relaxed control policies during the COVID-19 pandemic. Negative childhood experiences and bad mental status during the recovery period were harmful to coping with pandemic-related addictive internet use. SCIENTIFIC SIGNIFICANCE: Our findings profiled the general trend of addictive internet use and the vulnerable characteristics of its bad progression across different periods of the first wave of COVID-19 pandemic in China. Our findings provide valuable insights for preventing the long-term adverse effects of negative public events on Internet addiction.

Role of elective neck dissection in prognosis of N0M0 maxillary sinus squamous cell carcinoma: Insights from SEER database analysis.

BACKGROUND: The optimal management of cervical lymph nodes in N0M0 maxillary sinus squamous cell carcinoma (MSSCC) remains a subject of debate. This study aimed to investigate the impact of elective neck dissection (END) on the prognosis of N0M0 MSSCC patients and explore potential prognostic factors. METHODS: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was employed to minimize bias between the END and non-END groups. Cox regression analysis was performed to identify prognostic factors, and subgroup analyses were conducted based on patient characteristics. Furthermore, the optimal number of lymph nodes in END was determined using maximally selected test statistics. RESULTS: A total of 777 N0M0 MSSCC patients were included in the study. After PSM, patients who underwent END demonstrated significantly improved overall survival (OS) and cancer-specific survival (CSS) compared to those who did not undergo END (p < 0.05). Subgroup analyses revealed a favorable prognosis for patients receiving radiotherapy and END, with a hazard ratio of 0.729 (95% CI: 0.549-0.967; p = 0.029) for OS. Furthermore, patients with a lymph node count greater than 5 in END had significantly better OS and CSS compared to those with 5 or fewer lymph nodes (p = 0.013, p = 0.018, respectively). CONCLUSION: Our findings suggest that END provides a survival benefit for N0M0 MSSCC patients. Additionally, a lymph node count greater than 5 in END is associated with improved staging accuracy and better prognosis. Prospective research is needed to validate these findings and inform clinical decision-making for N0M0 MSSCC patients.

Intraparotid node metastasis affects the long-term survival of patients with resectable recurrent parotid gland carcinoma.

PURPOSE: The recurrence rate of parotid gland cancer is high, but research on the prognosis of recurrent parotid gland cancer (RPC) is relatively limited. We aim to determine the potential prognosis factors of RPC. STUDY DESIGN: Retrospective cohort analysis. SETTING: Tertiary cancer center. METHODS: We conducted a retrospective review from 2012 to 2021 on RPC patients treated at the China National Cancer Center (CNCC). To analyze the impact of various variables on overall survival (OS) after recurrence, a univariate and multivariate Cox proportional hazard model was employed. RESULTS: A total of 50/218 (23.0%) patients diagnosed with RPC and underwent surgery. The 5-year OS of all RPC patients in this cohort was 61.9%. 5 of 50 patients (10%) exhibited intraparotid node (IPN) metastasis. By univariate and multivariate analyses, we found that IPN metastasis was one of the prognostic factors of OS (p = 0.039) in RPC patients. The presence of IPN metastasis was also related to poor survival in individuals with negative cervical lymph nodes (CN0) (p = 0.011). In terms of the influence of surgical margins on prognosis, our findings revealed that RPC patients with negative margins exhibited a higher survival result than those with positive margins (p = 0.002). CONCLUSION: According to this study, IPN metastasis indicate a high incidence of mortality in recurrent parotid cancer patients. Particularly, in CN0 patients, the presence of IPN metastasis was associated with poor survival in CN0 patients.