Feasibility of free-breathing 19 F MRI image acquisition to characterize ventilation defects in CF and healthy volunteers at wash-in.

PURPOSE: To explore the feasibility of measuring ventilation defect percentage (VDP) using 19 F MRI during free-breathing wash-in of fluorinated gas mixture with postacquisition denoising and to compare these results with those obtained through traditional Cartesian breath-hold acquisitions. METHODS: Eight adults with cystic fibrosis and 5 healthy volunteers completed a single MR session on a Siemens 3T Prisma. 1 H Ultrashort-TE MRI sequences were used for registration and masking, and ventilation images with 19 F MRI were obtained while the subjects breathed a normoxic mixture of 79% perfluoropropane and 21% oxygen (O2 ). 19 F MRI was performed during breath holds and while free breathing with one overlapping spiral scan at breath hold for VDP value comparison. The 19 F spiral data were denoised using a low-rank matrix recovery approach. RESULTS: VDP measured using 19 F VIBE and 19 F spiral images were highly correlated (r = 0.84) at 10 wash-in breaths. Second-breath VDPs were also highly correlated (r = 0.88). Denoising greatly increased SNR (pre-denoising spiral SNR, 2.46 ± 0.21; post-denoising spiral SNR, 33.91 ± 6.12; and breath-hold SNR, 17.52 ± 2.08). CONCLUSION: Free-breathing 19 F lung MRI VDP analysis was feasible and highly correlated with breath-hold measurements. Free-breathing methods are expected to increase patient comfort and extend ventilation MRI use to patients who are unable to perform breath holds, including younger subjects and those with more severe lung disease.

Life-threatening airway obstruction due to retropharyngeal and cervicomediastinal hematomas following transjugular intrahepatic portosystemic shunt procedure for acute variceal bleeding in cirrhosis.

We report a case of life-threatening airway obstruction due to retropharyngeal-cervicomediastinal hematomas following transjugular intrahepatic portosystemic shunt or acute variceal bleeding in cirrhosis. Even though this is a rare complication, clinicians should maintain a high index of suspicion and evaluate and treat it promptly to prevent a fatal outcome.

Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism.

OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice. METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed. RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella. CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

Immobilized short-chain dehydrogenase/reductase on Fe3O4 particles acts as a magnetically recoverable biocatalyst component in patulin bio-detoxification system.

Patulin is one of the most important mycotoxins that contaminates fruit-derived products and causes acute or chronic toxicity in humans. In the present study, a novel patulin-degrading enzyme preparation was developed by taking a short-chain dehydrogenase/reductase and covalently linking it to dopamine/polyethyleneimine co-deposited magnetic Fe3O4 particles. Optimum immobilization provided 63% immobilization efficiency and 62% activity recovery. Moreover, the immobilization protocol substantially improved thermal and storage stabilities, proteolysis resistance, and reusability. Using reduced nicotinamide adenine dinucleotide phosphate as a cofactor, the immobilized enzyme exhibited a detoxification rate of 100% in phosphate-buffered saline and a detoxification rate of more than 80% in apple juice. The immobilized enzyme did not cause adverse effects on juice quality and could be magnetically separated quickly after detoxification to ensure convenient recycling. Moreover, it did not exhibit cytotoxicity against a human gastric mucosal epithelial cell line at a concentration of 100 mg/L. Consequently, the immobilized enzyme as a biocatalyst had the characteristics of high efficiency, stability, safety, and easy separation, establishing the first step in building a bio-detoxification system to control patulin contamination in juice and beverage products.

Incidence trends of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancers among males in Taiwan, 1980-2019: a population-based cancer registry study.

In a country with a high prevalence of cigarette smoking, betel chewing, and alcohol drinking, cancers of the oral cavity, nasopharynx, and larynx were the fourth, twelfth and seventeenth leading causes of cancer death, respectively, for men in 2020. We analyzed patients with head and neck cancer from 1980 to 2019 from the Taiwan Cancer Registration Database and discussed the annual average percent change, average percent change, age period, and birth cohort. Obvious period effects and birth effects are seen in oral, oropharyngeal, and hypopharyngeal cancer; however, the most significant period effect was seen between 1990 and 2009, which mainly reflects the consumption of betel nuts per capita. In addition, the period effect lessens after 2010 in oral cancer and hypopharyngeal cancers, while oropharyngeal cancers remain an obvious period effect, which results from the rising prevalence of HPV. Due to the high prevalence rate of betel quid chewing and cigarette smoking in the 1990s, the government executed several acts. As a result, the age-adjusted incidence rates of oral, oropharyngeal, and hypopharyngeal cancers have flattened since 2010, which can be explained by the declining cigarette smoking rate. The strict policy indeed shows an obvious effect on the head and neck cancer incidence rates, and we expect to see a further decline in the future.

Circular RNA circDLG1 (has_circ_0068706) functions as an oncogene in nonsmall cell lung cancer through regulating AKT/mTOR signaling and direct binding to miR-144.

Nonsmall cell lung cancer (NSCLC) is a major subtype of lung cancer, causing substantial cancer-related deaths worldwide. However, the molecular basis of NSCLC development and progression remains understudied. Recently, a circular RNA, circDLG1, has been implicated in carcinogenesis and cancer metastasis. Yet, how circDLG1 affects NSCLC progression has not been reported. Here this study aims to elucidate the role of circDLG1 in NSCLC. First, we found that circDLG1 was significantly upregulated in both the GEO dataset and NSCLC tissues. Next, we silenced the expression of circDLG1 in NSCLC cell lines. Knockdown of circDLG1 upregulated miR-144 and downregulated Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), resulting in suppression of the proliferation activity and metastasis ability of NSCLC. In addition, circDLG1 knockdown significantly decreased the expression of the mesenchymal markers, proliferating cell nuclear antigen (PCNA), and N-cadherin, while increasing the expression level of E-cadherin. In conclusion, we demonstrate that circDLG1 promotes the pathogenesis and progression of NSCLC by regulating the miR-144/AKT/mTOR signaling axis, providing potential diagnostic and therapeutic targets for designing innovative treatment strategies.

Comparison of crop productivity, economic benefit and environmental footprints among diversified multi-cropping systems in South China.

Diversified multi-cropping system with high productivity and low environmental costs is crucial for the development of sustainable agriculture in different regions. However, the information on this practice has still been limited in the South China. This study compared different diversified multi-cropping systems including peanut-rice-fallow (P-R-F), peanut-rice-ryegrass (P-R-R), soybean-rice-ryegrass (S-R-R), feed corn-rice-milk vetch (FC-R-M), sweet corn-rice-milk vetch (SC-R-M) and zucchini -rice-milk vetch (Z-R-M), with the conventional double-rice system (CK). A newly proposed agricultural environmental footprint index (EFI) framework was introduced to quantify the comprehensive environmental costs of different systems. Results indicated that the annual productivities of P-R-R and FC-R-M rotation systems significantly increased by 39.91 % and 25.06 %, respectively, compared to the CK. The economic benefits of P-R-R and FC-R-M were 53.71 % and 16.67 % higher than the CK, respectively, with significant differences. The EFIs based on unit farmland area, crop productivity and economic benefit of the P-R-R and FC-R-M systems were 17.07 %-40.68 % lower than the CK, respectively, showing the lower environmental costs. Therefore, the P-R-R and FC-R-M were recommended as alternatives of double-rice cropping in the South China. In addition, the results indicated that the fertilization and irrigation practices were the key points for improving the rotation systems. This study provided valuable information for the transition of rice-based cropping system in South China. It was also a reference for the development of sustainable agriculture in the world's subtropical agricultural system.

"Extended Frontalis Muscle Advancement Technique for Severe Congenital Blepharoptosis".

BACKGROUND: The conventional frontalis muscle advancement technique still has some disadvantages, such as residual lagophthalmos, eyebrow ptosis, eyelid contour abnormality, and under-correction. This article describes the authors' extended frontalis muscle advancement technique that takes extensive subcutaneous separation through the eyelid crease incision for the treatment of severe congenital blepharoptosis. METHODS: A retrospective review was performed that included patients with severe congenital ptosis who underwent extended frontalis muscle advancement technique from April of 2019 to April of 2021. Preoperative evaluation included age, sex, and margin reflex distance 1 (MRD1), levator function, and lagophthalmos. Postoperative evaluation including correction result, closure function of eyelid, cosmetic result was performed at the last follow-up. RESULTS: From April of 2019 to April of 2021, a total of 102 patients (137 eyes) who underwent extended frontalis muscle advancement technique were included in the study. The mean postoperative MRD1 in unilateral and bilateral ptosis patients was 3.84 ± 0.60 mm and 3.86 ± 0.56, respectively, and 126 eyes (92.0 percent) showed successful correction. Postoperatively, the mean residual lagophthalmos was 0.88 ± 1.40 mm, and 127 eyes (92.7 percent) showed excellent or good eyelid closure function. The average score of cosmetic results was 8.29 ± 1.34, and 94 patients (92.2 percent) had an excellent or good cosmetic result. CONCLUSIONS: Extensive subcutaneous separation relieves the mutual restriction between the forehead skin and frontalis muscle. The extended frontalis muscle advancement technique is effective in correcting severe congenital ptosis, while minimizing under-correction, residual lagophthalmos, eyelid contour abnormality and eyebrow ptosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

[Acupoints compatibility rules of acupuncture for depression disease based on data mining technology].

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24+), Zusanli (ST 36), Hegu (LI 4), Sishencong (EX-HN 1) and Taixi (KI 3), etc. The frequently involved meridians were the governor vessel, foot-taiyang bladder meridian, foot-taiyin spleen meridian, and foot-jueyin liver meridian. The frequency of the special acupoints from high to low was crossing points, five-shu points, yuan-primary points, back-shu points, luo-connecting points, and eight confluent points, etc, which were often used in combination with "Baihui (GV 20)-Yintang (GV 24+)" (the highest degree of association). At the same time, the analysis of the co-occurrence network of depression diseases and acupoints showed that the core acupoints group of acupuncture for depression diseases were Baihui (GV 20), Taichong (LR 3), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6) and Sanyinjiao (SP 6). In conclusion, acupuncture treatment for depression diseases has gradually formed a rule of acupoint compatibility, with special acupoint as the main body and "unblocking the governor vessel, and regulating the spirit and qi " as the main therapeutic principle.

Trends in the evolution of intronless genes in Poaceae.

Intronless genes (IGs), which are a feature of prokaryotes, are a fascinating group of genes that are also present in eukaryotes. In the current study, a comparison of Poaceae genomes revealed that the origin of IGs may have involved ancient intronic splicing, reverse transcription, and retrotranspositions. Additionally, IGs exhibit the typical features of rapid evolution, including recent duplications, variable copy numbers, low divergence between paralogs, and high non-synonymous to synonymous substitution ratios. By tracing IG families along the phylogenetic tree, we determined that the evolutionary dynamics of IGs differed among Poaceae subfamilies. IG families developed rapidly before the divergence of Pooideae and Oryzoideae and expanded slowly after the divergence. In contrast, they emerged gradually and consistently in the Chloridoideae and Panicoideae clades during evolution. Furthermore, IGs are expressed at low levels. Under relaxed selection pressure, retrotranspositions, intron loss, and gene duplications and conversions may promote the evolution of IGs. The comprehensive characterization of IGs is critical for in-depth studies on intron functions and evolution as well as for assessing the importance of introns in eukaryotes.

Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program.

Objectives: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC. Materials and Methods: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls. Results: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise. Discussion: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes. Conclusion: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

Covid-19 Pandemic Strategy for Treatment of Acute Uncomplicated Appendicitis with Antibiotics- Risk Categorization and Shared Decision-Making.

BACKGROUND: During the Coronavirus disease 2019 (COVID-19) pandemic, a protocol was adopted by our department on antibiotics treatment for Acute Uncomplicated Appendicitis (AUA). Our study aimed to determine the feasibility and safety of non-operative treatment (NOT), compared to upfront laparoscopic appendectomy (LA), for AUA in children during the pandemic. METHOD: Our prospective comparative study was conducted from May 1, 2020 to January 31, 2021. Patient selection criteria included: age ≥5 years, abdominal pain duration ≤48 h, ultrasound (US)/Computered Tomography scan confirmation of AUA, US appendiceal diameter 6-11 mm with no features of perforation/abscess collection and no faecolith. For NOT patients, intravenous antibiotics were administered for 24-48 h followed by oral for 10-day course. Comparison was performed between patients whose parents preferred NOT to those who opted for up-front appendectomy. Primary outcomes were NOT success at index admission, early and late NOT failure rates till 27 months. Secondary outcomes were differences in complication rate, hospital length of stay (LOS) and cost between groups. RESULTS: 77 patients were recruited: 43 (55.8%) underwent NOT while 34 (44.2%) patients opted for LA. Success of NOT at index admission was 90.7% (39/43). Overall, NOT failure rate at 27 months' follow-up was 37.2% (16/43). Of the NOT failures, 1 appendix was normal on histology while only 1 was perforated. There were no significant differences in secondary outcomes between both groups except for LOS of late NOT failure. Cost for upfront LA was nearly thrice that of NOT. CONCLUSION: Our stringent COVID protocol together with shared decision-making with parents is a safe and feasible treatment option during a crisis situation. LEVEL OF EVIDENCE: Treatment study, Level II.

'On Water'-Promoted Three-Component Tandem Michael Addition/D-A Cycloaddition Reaction to Construct Polycyclic N-Heterocycles Derivatives.

'On Water'-promoted the three-component tandem Michael addition/D-A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N-heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats.

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease (PD). However, the mechanisms underlying this association remain unclear. In the present study, we found that high glucose (HG) levels in the cerebrospinal fluid (CSF) of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine (6-OHDA) on the development of motor disorders, and the damage to the nigrostriatal dopaminergic neuronal pathway. In vitro, HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor (NGF) (NGF-PC12). Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle (TCA cycle) activity, which was closely related to abnormal mitochondrial fusion, thus resulting in mitochondrial loss. Interestingly, HG-induced upregulation of pyruvate kinase M2 (PKM2) combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells. In addition, we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA. Furthermore, we found that shikonin (SK), an inhibitor of PKM2, restored the mitochondrial number, promoted TCA cycle activity, reversed hyperglycolysis, enhanced the tolerance of cultured neurons to 6-OHDA, and reduced the risk of PD in diabetic rats. Overall, our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upregulation of PKM2, leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA. Thus, the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Protective effect of antihypertensive drugs on the risk of Parkinson's disease lacks causal evidence from mendelian randomization.

Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson's disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD. Methods: Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure. SBP-associated variants either located within encoding regions or associated with the expression of AHM targets were selected and then scaled to proxy therapeutic inhibition of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, calcium channel blockers, and thiazides. Positive control analyses on coronary heart disease (CHD) and stroke were conducted to validate the IV selection. Summary data from GWAS for PD risk and PD age at onset (AAO) were used as outcomes. Results: In positive control analyses, genetically determined BP traits and AHMs closely mimicked the observed causal effect on CHD and stroke, confirming the validity of IV selection methodology. In primary analyses, although genetic proxies identified by "encoding region-based method" for ß-blockers were suggestively associated with a delayed PD AAO (Beta: 0.115; 95% CI: 0.021, 0.208; p = 1.63E-2; per 10-mmHg lower), sensitivity analyses failed to support this association. Additionally, MR analyses found little evidence that genetically predicted BP traits, overall AHM, or other AHMs affected PD risk or AAO. Conclusion: Our data suggest that BP and commonly prescribed AHMs may not have a prominent role in PD etiology.

A portable thermostatic molecular diagnosis device based on high-efficiency photothermal conversion material for rapid field detection of SARS-CoV-2.

The outbreak of the novel coronavirus (SARS-CoV-2) has seriously harmed human health and economic development worldwide. Studies have shown that timely diagnosis and isolation are the most effective ways to prevent the spread of the epidemic. However, the current polymerase chain reaction (PCR) based molecular diagnostic platform has the problems of expensive equipment, high operation difficulty, and the need for stable power resources support, so it is difficult to popularize in low-resource areas. This study established a portable (<300 g), low-cost (<$10), and reusable molecular diagnostic device based on solar energy photothermal conversion strategy, which creatively introduces a sunflower-like light tracking system to improve light utilization, making the device suitable for both high and low-light areas. The experimental results show that the device can detect SARS-CoV-2 nucleic acid samples as low as 1 aM within 30 min.

B cells promote granulomatous inflammation during chronic Mycobacterium tuberculosis infection in mice.

The current study reveals that in chronic TB, the B cell-deficient µMT strain, relative to wild-type (WT) C57BL/6 mice, displays in the lungs lower levels of inflammation that are associated with decreased CD4+ T cell proliferation, diminished Th1 response, and enhanced levels of interleukin (IL)-10. The latter result raises the possibility that B cells may restrict lung expression of IL-10 in chronic TB. These observations are recapitulated in WT mice depleted for B cells using anti-CD20 antibodies. IL-10 receptor (IL-10R) blockade reverses the phenotypes of decreased inflammation and attenuated CD4+ T cell responses in B cell-depleted mice. Together, these results suggest that in chronic murine TB, B cells, by virtue of their capacity to restrict expression of the anti-inflammatory and immunosuppressive IL-10 in the lungs, promote the development of a robust protective Th1 response, thereby optimizing anti-TB immunity. This vigorous Th1 immunity and restricted IL-10 expression may, however, allow the development of inflammation to a level that can be detrimental to the host. Indeed, decreased lung inflammation observed in chronically infected B cell-deficient mice, which exhibit augmented lung IL-10 levels, is associated with a survival advantage relative to WT animals. Collectively, the results reveal that in chronic murine TB, B cells play a role in modulating the protective Th1 immunity and the anti-inflammatory IL-10 response, which results in augmentation of lung inflammation that can be host-detrimental. Intriguingly, in tuberculous human lungs, conspicuous B cell aggregates are present in close proximity to tissue-damaging lesions manifesting necrosis and cavitation, suggesting the possibility that in human TB, B cells may contribute to the development of exacerbated pathology that is known to promote transmission. Since transmission is a major hindrance to TB control, investigating into whether B cells can shape the development of severe pulmonic pathological responses in tuberculous individuals is warranted.

A Bispecific Peptide-Polymer Conjugate Bridging Target-Effector Cells to Enhance Immunotherapy.

Peptide-based immune checkpoint inhibitors exhibit remarkable therapeutic benefits although their application is hindered by quick blood clearance and low affinity with receptors. The modification of the peptides into artificial antibodies is an ideal platform to solve these problems, and one of the optional pathways is the conjugation of peptides with a polymer. More importantly, the bridging effect, mediated by bispecific artificial antibodies, could promote the interaction of cancer cells and T cells, which will benefit cancer immunotherapy. Herein, a bispecific peptide-polymer conjugate (octa PEG-PD1-PDL1) is prepared by simultaneously conjugating PD1-binding and PDL1-binding peptides onto 8-arm-PEG. octa PEG-PD1-PDL1 bridges T cells and cancer cells and thus enhances T cell-mediated cytotoxicity against cancer cells. Meanwhile, the tumor-targeting octa PEG-PD1-PDL1 increases the infiltration of cytotoxic T lymphocytes in tumors and reduces their exhaustion. It effectively activates the tumor immune microenvironment and exerts a potent antitumor effect against CT26 tumor models with a tumor inhibition rate of 88.9%. This work provides a novel strategy to enhance tumor immunotherapy through conjugating bispecific peptides onto a hyperbranched polymer to effectively engage target-effector cells.

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single- Center Study.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an ORR of 81.3% and a disease control rate of 87.5%. The median PFS was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95%CI 13.6-46.4), the 5-year overall survival was 77% (95% CI 66-88%) in all patients. Conclusion: Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.