Compatible camouflage for dual-band guided-laser radar and infrared via a metamaterial perfect absorber.

Laser-guided detector and infrared detection have attracted increasing attention in a wide range of research fields, including multispectral detection, radiative cooling, and thermal management. Previously reported absorbers presented shortcomings of lacking either tunability or compatibility. In this study, a metamaterial perfect absorber based on a Helmholtz resonator and fractal structure is proposed, which realizes tunable perfect absorptivity (α 1.06µ m >0.99,α 10.6µ m >0.99) of guided-laser radar dual operating bands (1.06 µm and 10.6 µm) and a low infrared average emissivity (ε¯3-5µ m =0.03,ε¯8-14µ m =0.31) in two atmospheric windows for compatible camouflage. The proposed perfect absorber provides a dynamically tunable absorptivity without structural changes and can be applied to optical communication, military stealth or protection, and electromagnetic detection.

Opinion Mining by Convolutional Neural Networks for Maximizing Discoverability of Nanomaterials.

The scientific literature contains valuable information that can be used for future applications, but manual analysis presents challenges due to its size and disciplinary boundaries. The prevailing solution involves natural language processing (NLP) techniques such as information retrieval. Nonetheless, existing automated systems primarily provide either statistically based shallow information or deep information without traceability, thereby falling short of delivering high-quality and reliable insights. To address this, we propose an innovative approach of leveraging sentiment information embedded within the literature to track the opinions toward materials. In this study, we integrated material knowledge into text representation and constructed opinion data sets to hierarchically train deep learning models, named as Scientific Sentiment Network (SSNet). SSNet can effectively extract knowledge from the energy material literature and accurately categorize expert opinions into challenges and opportunities (94% and 92% accuracy, respectively). By incorporating sentiment features determined by SSNet, we can predict the ranking of emerging thermoelectric materials with a 70% correlation to experimental outcomes. Furthermore, our model achieves a commendable 68% accuracy in predicting suitable nanomaterials for atomic layer deposition (ALD) over time. These promising results offer a practical framework to extract and synthesize knowledge from the scientific literature, thereby accelerating research in the field of nanomaterials.

Identification of novel biomarkers based on lipid metabolism-related molecular subtypes for moderately severe and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.

Recruitment and retention of adolescents for an ecological momentary assessment measurement burst mental health study: The MHIM engagement strategy.

INTRODUCTION: Recruitment and long-term retention of adolescent participants in longitudinal research are challenging and may be especially so in studies involving remote measurement and biosampling components. The ability to effectively recruit and retain participants can be supported by the use of specific evidence-based engagement strategies that are built in from the earliest stages. METHODS: Informed by a review of the evidence on effective engagement strategies and consultations with adolescents (via two Young Person Advisory Groups [YPAGs]; ages 11-13 and 14-17), the current protocol describes the planned participant engagement strategy for the Mental Health in the Moment Study: a multimodal measurement burst study of adolescent mental health across ages 11-19. RESULTS: The protocol incorporates engagement strategies in four key domains: consultations/co-design with the target population, incentives, relationship-building and burden/barrier reduction. In addition to describing general engagement strategies in longitudinal studies, we also discuss specific concerns regarding engagement in data collection methods such as biosampling and ecological momentary assessment where a paucity of evidence exists. CONCLUSION: Engagement strategies for adolescent mental health studies should be based on existing evidence and consultations with adolescents. We present our approach in developing the planned engagement strategies and also discuss limitations and future directions in engaging adolescents in longitudinal research. PATIENT OR PUBLIC CONTRIBUTION: The study design for this project places a strong emphasis on the active engagement of adolescents throughout its development. Specifically, the feedback and suggestions provided by the YPAGs have been instrumental in refining our strategies for maximising the recruitment and retention of participants.

Network structure of adolescent social, emotional, and behavioral difficulties and their differential relationships with suicidality.

BACKGROUND: Social, emotional, and behavioral difficulties (SEBDs) tend to develop during adolescence. Their presence and especially co-occurrence induce numerous disrupting consequences, including suicidality. A recently developed network analysis is suitable to investigate the symptom-level structure of comorbid psychopathology. Rather than pairwise comorbidity networks, the current study investigated a comprehensive network of SEBDs at the symptom level and explored the differential relationships between symptoms of SEBDs and suicidality. METHODS: Recruited from four public schools in China, a sample of adolescents (N = 6974, mean age = 15.84, 50.1% boys) were assessed with the Strengths and Difficulties Questionnaire (SDQ) and one suicidality-related item. The cross-sectional network structure of the SEBD symptoms was investigated. The differential associations between individual symptoms of SEBDs and suicidality were also explored with a relative importance analysis. RESULTS: The results showed that constantly fidgeting, worry a lot, unhappy, down-hearted, tearful, and easily scared emerged as the most central symptoms in the network of SEBDs. Worry a lot, constantly fidgeting, lose my temper, and being bullied served as bridge symptoms, connecting various domains of SEBDs. In addition, the centrality of symptoms was positively associated with the variance shared with suicidality, with worry a lot and unhappy, down-hearted, and tearful explaining a large portion of the variance of suicidality. CONCLUSIONS: Taken together, the results were indicative of close connections among emotional, hyperactivity-inattention, peer, and conduct aspects of adolescent mental health difficulties, as well as the central role of emotional difficulties in the SEBDs network.

Discovery of N-Acyl Amino Acids and Novel Related N-, O-Acyl Lipids by Integrating Molecular Networking and an Extended In Silico Spectral Library.

Research on novel bioactive lipids has garnered increasing interest. Although lipids can be identified by searching mass spectral libraries, the discovery of novel lipids remains challenging as the query spectra of such lipids are not included in libraries. In this study, we propose a strategy to discover novel carboxylic acid-containing acyl lipids by integrating molecular networking with an extended in silico spectral library. Derivatization was performed to improve the response of this method. The tandem mass spectrometry spectra enriched by derivatization facilitated the formation of molecular networking and 244 nodes were annotated. We constructed consensus spectra for these annotations based on molecular networking and developed an extended in silico spectral library based on these consensus spectra. The spectral library included 6879 in silico molecules covering 12,179 spectra. Using this integration strategy, 653 acyl lipids were discovered. Among these, O-acyl lactic acids and N-lactoyl amino acid-conjugated lipids were annotated as novel acyl lipids. Compared with conventional methods, our proposed method allows for the discovery of novel acyl lipids, and extended in silico libraries significantly increase the size of the spectral library.

Analysis of temporal metabolic rewiring for human respiratory syncytial virus infection by integrating metabolomics and proteomics.

INTRODUCTION: Human respiratory syncytial virus (HRSV) infection causes significant morbidity, and no effective treatments are currently available. Viral infections induce substantial metabolic changes in the infected cells to optimize viral production. Metabolites that reflect the interactions between host cells and viruses provided an opportunity to identify the pathways underlying severe infections. OBJECTIVE: To better understand the metabolic changes caused by HRSV infection, we analyzed temporal metabolic profiling to provide novel targets for therapeutic strategies for inhaled HRSV infection. METHODS: The epithelial cells and BALB/c mice were infected with HRSV. Protein and mRNA levels of inflammation factors were measured by using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Untargeted metabolomics, lipidomics and proteomics were performed using liquid chromatography coupled with mass spectrometry to profile the metabolic phenotypic alterations in HRSV infection. RESULTS: In this study, we evaluated the inflammatory responses in vivo and in vitro and investigated the temporal metabolic rewiring of HRSV infection in epithelial cells. We combined metabolomics and proteomic analyses to demonstrate that the redox imbalance was further provoked by increasing glycolysis and anaplerotic reactions. These responses created an oxidant-rich microenvironment that elevated reactive oxygen species levels and exacerbated glutathione consumption. CONCLUSION: These observations indicate that adjusting for metabolic events during a viral infection could represent a valuable approach for reshaping the outcome of infections.

Development and validation of the systemic lupus erythematous scale amongst the system of quality of life instruments for chronic diseases QLICD-SLE (V2.0).

OBJECTIVE: The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). METHODS: The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. RESULTS: Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test-retest correlation coefficients exceeded 0.71, and Cronbach's alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P < 0.05), indicating reasonable responsiveness. CONCLUSION: The QLICD-SLE (V2.0) appears to be a valid and reliable instrument for assessing the quality of life in patients with SLE.

Effect of Comprehensive Psychological Intervention on Negative Emotions and Quality of Life in Patients with Acute Myocardial Infarction.

Although acute myocardial infarction (AMI) currently has a high survival rate, the treatment and prognosis are still diffuse negative life events for patients, which will affect their quality of life (QOL) and psychological health. Based on an integrated physiological-psychological-social-medical model, it is necessary to design an intervention program for safeguarding the physical and mental health of AMI patients.This study aimed to explore the influence of psychological intervention on negative emotions and QOL of AMI patients using a randomized controlled trial (RCT) design.Based on convenience sampling and double-blinded group assignment, 101 patients from August 2019 to January 2020 were randomly divided into 2 groups. An intervention group received comprehensive psychological intervention, while a control group received general supportive nursing. Both groups answered questionnaires before and after the intervention, including assessments of anxiety, depression, and QOL.Before the intervention, there were no significant differences between the groups. After intervention, anxiety and depression in the intervention group (n = 48) were significantly lower (P < 0.001) and QOL was markedly improved (P < 0.05) compared to that of the control group (n = 53).Comprehensive psychological intervention contributed to ameliorate negative emotions, enhance confidence in treatment, and improve the QOL of AMI patients.

Mitogen-activated protein kinase-interacting kinase 1 is involved in mTOR-mediated pancreatic exocrine function of bovine pancreatic acinar cells with leucine supply.

Leucine improves the exocrine capacity of the cow pancreas, but the mechanism was not revealed clearly. Mitogen-activated protein kinase-interacting kinase 1 (MNK1) is a pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance. We aimed to investigate the MNK1 gene and protein expression profiles among various organs or tissues of dairy cows and to demonstrate the mechanism by which leucine-stimulated MNK1 regulates pancreatic exocrine function. Firstly, the expression profiles of MNK1 protein and gene in the tissues and organs of dairy cows were measured using immunohistochemistry and RT-qPCR methods. Next, an in vitro model of cultured Holstein dairy calf pancreatic acinar cells was used to detect the role of MNK1 during pancreatic enzymes release which is stimulated by leucine. Cells were incubated in culture medium containing L-leucine (0.45 mM) for 180 min, and samples were collected hourly, with the control not containing L-leucine (0 mM). MNK1 was expressed at very high levels in the pancreatic tissue of dairy cows. Leucine supplementation increased the α-amylase level but not lipase level at three time-points (60, 120, and 180 min), and the interaction between treatments and times was significant only for α-amylase. Leucine treatment enhanced (P < 0.05) the phosphorylation of MNK1 and eIF4E. In addition, inhibition of MNK1 decreased leucine-mediated α-amylase and lipase release (P < 0.05) and the phosphorylation of Mnk1 and eIF4E but did not affect (P > 0.05) the phosphorylation of the mTOR signalling pathway factors 4EBP1 and S6K1. In summary, MNK1 is a key regulator of pancreatic exocrine function, which is regulated by leucine in the pancreas of dairy cows.

[Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study].

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

Class â histone deacetylase inhibitor regulate of Mycobacteria-Driven guanylate-binding protein 1 gene expression.

Guanylate-binding proteins (GBPs) are a class of interferon (IFN)-stimulated genes with well-established activity against viruses, intracellular bacteria, and parasites. The effect of epigenetic modification on GBP activity upon Mycobacterium tuberculosis (Mtb) infection is poorly understood. In this study, we found that Mtb infection can significantly increase the expression of GBPs. Class Ⅰ histone deacetylase inhibitor (HDACi) MS-275 can selectively inhibit GBP1 expression, ultimately affecting the release of inflammatory cytokines IL-1ß and suppressing Mtb intracellular survival. Moreover, interfering with GBP1 expression could reduce the production of IL-1ß and the level of cleaved-caspase-3 in response to Mtb infection. GBP1 silencing did not affect Mtb survival. Besides, using the bisulfite sequencing PCR, we showed that the CpG site of the GBP1 promoter was hypermethylated, and the methylation status of the GBP1 promoter did not change significantly upon Mtb infection. Overall, this study sheds light on the role of GBP in Mtb infection and provides a link between epigenetics and GBP1 activity.

Report on antennal sensilla of Aphelocheirus ellipsoideus (Hemiptera, Heteroptera, Aphelocheiridae).

The comparative morphology study on antennal sensilla of Aphelocheirus ellipsoideus from the family Aphelocheiridae, carried out with the use of a scanning electron microscope, is provided. Five main types of mechano-, chemo-, and thermo-hygroreceptive sensilla with two subtypes of sensilla basiconica were found and described on their surface, including sensilla trichodea, campaniformia, basiconica, ampullacea, and plate-like. Antennal sensilla of A. ellipsoideus on macropterous and brachypterous forms were different.

Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.

Many mutant p53 proteins (mutp53s) exert oncogenic gain-of-function (GOF) properties, but the mechanisms mediating these functions remain poorly defined. We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells. Conversely, downregulation of GOF mutp53s enhances AMPK activation under energy stress, decreasing the activity of the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 and inhibiting aerobic glycolytic potential and invasive cell growth. Under conditions of energy stress, GOF mutp53s, but not wild-type p53, preferentially bind to the AMPKα subunit and inhibit AMPK activation. Given the importance of AMPK as an energy sensor and tumor suppressor that inhibits anabolic metabolism, our findings reveal that direct inhibition of AMPK activation is an important mechanism through which mutp53s can gain oncogenic function.

The relationship between peer victimization and social anxiety among adolescents: a moderated mediation model with cognitive flexibility and affect intensity.

Building a friendship with peers is an important developmental task. However, peer victimization and social anxiety are among the most disturbing problems and have impaired adolescents' adaptive development. A total of 942 adolescents completed the survey. The results showed that peer victimization was related to social anxiety and that this effect was mediated by cognitive flexibility and moderated by affect intensity. Specifically, the damage of peer victimization and social anxiety was aggrevated for those with high levels of affect intensity. The current study provides evidence for the association between peer victimization and social anxiety. It contributes to the literature by clarifying the equivocal findings and uncovering the underlying mechanisms of the relationship between peer victimization and social anxiety. In the future, researchers and teachers should pay attention to adolescents' peer social status as early as possible, especially for adolescents with higher levels of affect intensity.

Utilizing network analysis to understand the structure of depression in Chinese adolescents: Replication with three depression scales.

Depression involves a heterogenous collection of symptoms. Network perspective views depressive symptoms as an interrelated network. The current study aimed to replicate network analyses on adolescent depression in three samples assessed with three instruments to examine the consistency of network structures and also examine the variance of networks between genders. Three samples of adolescents (total N = 4375, mean age = 15, 49.1% boys) were assessed with PHQ-9, SMFQ and CDI, respectively. Network analyses were carried out on depression symptoms. Network stability, node centrality and network comparisons between genders were examined. Three networks were reliably stable. Sadness and self-hatred were unanimously identified to be central symptoms of adolescent depression in three networks. In addition, fatigue, no good, everything wrong and loneliness also appeared to be central in specific networks. Among three depression networks, PHQ-9 network demonstrated gender difference in network structure. The current study is exploratory in nature. The differences in three networks can be due to various samples or different node inclusions. Further, the study is cross-sectional precluding causal interpretation and the samples are nonclinical. Besides "hallmark" symptom sadness, self-hatred was also identified unanimously in three networks, which demonstrated the significant role self-worth played in adolescent depression. The results also suggested that differences in node inclusion may have influence on the network structure. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03201-z.

The Inconsistent and Inadequate Reporting Of Immune-Related Adverse Events in PD-1/PD-L1 Inhibitors: A Systematic Review of Randomized Controlled Clinical Trials.

BACKGROUND: Immune-related adverse events (irAEs) are of great interest and importance in clinical practice, and many deficiencies and controversies have been noted in the reporting of irAEs. Herein, we aimed to evaluate the current status of irAE reporting in randomized controlled clinical trials (RCTs) of PD-1/PD-L1 inhibitors and to attempt to explain and solve the current pitfalls associated with this reporting. MATERIALS AND METHODS: We conducted a systematic review across multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library. The RCTs that compared PD-1/PD-L1 inhibitors with standard treatments were included. The Harms extension of the Consolidated Standards of Reporting Trials (CONSORT) was used to evaluate the completeness of irAE reporting. RESULTS: A total of 44 articles and 23,759 patients were included in the analysis. The terminology of the irAEs changed over time (p = .01) and was different among immune checkpoint inhibitors (ICIs) (p = .005). Twenty-two of the studies provided a definition of irAE, but only four of them concretely addressed this definition. The incidence of any grade of irAEs ranged from 16.9% to 96%, whereas grade 3-4 irAE ranged from 2% to 23%. The RCTs with combined therapy exhibited a higher incidence of grade 3-4 irAEs (p = .012). Thirty-two studies reported irAEs in the control arms, whereas seven studies reported irAEs only in the experimental arms. Respiratory, endocrine, and gastrointestinal disorders were the most commonly reported irAEs. IrAEs were generally neglected in the introduction or conclusion sections in all of the study reviews and were never subjected to subgroup analyses. Moreover, withdrawals due to severe irAEs, as well as clarifications of the irAE collection methods, were also poorly reported. RCTs using combination therapies in the experimental arms were associated with a higher reporting quality (p = .032). However, the completeness of the reporting did not improve over the last 5 years (p = .076). CONCLUSION: The reporting of irAEs was inadequate, and there are still inconsistencies and controversies in the reporting of irAEs. In the future, authors should be encouraged to adhere to the Harms extension of the CONSORT statement. IMPLICATIONS FOR PRACTICE: PD-1/PD-L1 inhibitors profoundly changed the landscape of cancer treatment, and thousands of randomized controlled clinical trials (RCTs) were active or completed over the past decade. However, different from chemotherapy or targeted therapy, the profile of immune-related adverse effects (irAE) was unique. An understanding of irAEs is developed mainly from clinical trials; however, inconsistencies and controversies between trials were noted. This study primarily reviewed the evolution of irAE terminology and definitions and evaluated the reporting quality of each RCT. It was found that RCTs using combined immunotherapy were associated with higher quality of irAE reporting. This article identifies the controversies and deficiencies in current irAE reporting and provides possible explanations and suggestions for these inadequacies.

Developmental validations of a self-developed 39 AIM-InDel panel and its forensic efficiency evaluations in the Shaanxi Han population.

Most of insertion/deletion polymorphisms are diallelic molecular markers characterized as small amplicon sizes, high inter-population diversities, and low mutation rates, which make them the promising genetic markers in biogeographic ancestor inference field. The developmental validations of a 39 ancestry informative marker-insertion/deletion (AIM-InDel) panel and the genetic polymorphic investigations of this panel were performed in the Shaanxi Han population of China. The developmental validation included the optimizations of PCR-related indicators, repeatability, reproducibility, precision, accuracy, sensitivity, species specificity, stability of the panel, and the abilities in analyzing degraded, casework, and mixture samples, and the present results demonstrated that this 39 AIM-InDel panel was robust, sensitive, and accurate. For the population diversity analyses, the combined discrimination power value of 38 AIM-InDel loci except for rs36038238 locus was 0.999999999931257, indicating that this novel panel was highly polymorphic, biogeographic informative, and could be also used in individual identifications in the Shaanxi Han population.

Cervical lymph node enlargement as the initial manifestation of rectal cancer.

BACKGROUND: Colorectal cancer is a very common malignant tumor worldwide. The clinical manifestations of advanced colorectal cancer include the changes in bowel habits, hematochezia, diarrhea, local abdominal pain and other symptoms. However, the colorectal cancer with an initial symptom of cervical lymph node enlargement is extremely rare. In this article, we report a case of rectal cancer presenting with cervical lymph nodes enlargement as the initial symptom. CASE PRESENTATION: A 57-year-old woman was admitted to our hospital for cervical lymph node enlargement which was accidentally detected during physical examination. Computed tomography scan revealed multiple enlarged lymph nodes in the neck. Cervical ultrasound showed normal thyroid gland and multiple left supraclavicular lymph nodes enlargement. The patient underwent lymph nodes biopsy and pathologic results showed metastatic adenocarcinoma. The subsequent lower gastrointestinal endoscopy revealed a mucosal bulge lesion located at rectus and biopsy revealed adenocarcinoma. The patient underwent rectal cancer resection. She is alive with no evidence of recurrence or new tumors 2 years after surgery. CONCLUSIONS: Cervical lymph node metastasis is a rare metastatic way in colorectal cancer. This is the first case of rectal cancer presenting with cervical lymph nodes metastases as the initial symptom. Surgical resection combined with postoperative chemotherapy improved long-term prognosis of the patient. This rare metastatic way of rectal cancer should be paid attention for clinicians.

Heterogeneous constitutional mismatch repair deficiency with MSH6 missense mutation clinically benefits from pembrolizumab and regorafenib combination therapy: a case report and literature review.

BACKGROUND: Germline DNA mismatch repair (MMR) gene aberrations are associated with colorectal cancer (CRC) predisposition and high tumor mutation burden (TMB-H), with increased likelihood of favorable response to immune checkpoint inhibitors (ICIs). CASE PRESENTATION: We present a 32-year old male patient diagnosed with constitutional MMR deficiency (CMMRD) CRC whose MMR immunohistochemistry (IHC) revealed inconsistent results from two tumor blocks. Targeted sequencing of two tumor specimens used in MMR-IHC and plasma-derived circulating tumor DNA consistently revealed the detection of bi-allelic germline MSH6 c.3226C > T (p.R1076C) mutation, TMB-H as well as the genetic heterogeneity of the tumor samples. Unexpectedly, both blocks were microsatellite stable (MSS) after PCR confirmation. Interestingly, the patient failed to show response to ICI monotherapy or dual therapy, but clinically benefitted from combined therapy of ICI pembrolizumab plus multi-kinase inhibitor regorafenib. CONCLUSION: Our case reported a CMMRD patient with heterogeneous MMR results who showed complicated response to ICIs, highlighting the importance of accurate diagnosis using targeted sequencing with multiple specimens to reveal the possible mechanism of response to ICI in patients with CMMRD.