Electrochemical cytosensor utilizing tetrahedral DNA/bimetallic AuPd holothurian-shaped nanoparticles for ultrasensitive non-destructive detection of circulating tumor cells.

As a real-time fluid biopsy method, the detection of circulating tumor cells (CTCs) provides important information for the early diagnosis, precise treatment, and prognosis of cancer. However, the low density of CTCs in the peripheral blood hampers their capture and detection with high sensitivity and selectivity using currently available methods. Hence, we designed a sandwich-type electrochemical aptasensor that utilizes holothurian-shaped AuPd nanoparticles (AuPd HSs), tetrahedral DNA nanostructures (TDNs), and CuPdPt nanowire networks (NWs) interwoven with a graphdiyne (GDY) sheet for ultrasensitive non-destructive detection of MCF-7 breast cancer cells. CuPdPt NW-GDY effectively enhanced the electron transfer rate and coupled with the loaded TDNs. The TDNs could capture MCF-7 cells with precision and firmness, and the resulting composite complex was combined with AuPd HSs to form a sandwich-type structure. This novel aptasensor showed a linear range between 10 and 106 cells mL-1 and an ultralow detection limit of 7 cells mL-1. The specificity, stability, and repeatability of the measurements were successfully verified. Moreover, we used benzonase nuclease to achieve non-destructive recovery of cells for further clinical studies. According to the results, our aptasensor was more sensitive measuring the number of CTCs than other approaches because of the employment of TDNs, CuPdPt NW-GDY, and AuPd HSs. We designed a reliable sensor system for the detection of CTCs in the peripheral blood, which could serve as a new approach for cancer diagnosis at an early stage.

Emerging trends in CDs@hydrogels composites: from materials to applications.

Carbon dots (CDs) are nanoscale carbon materials with unique optical properties and biocompatibility. Their applications are limited by their tendency to aggregate or oxidize in aqueous environments. Turning weakness to strengths, CDs can be incorporated with hydrogels, which are three-dimensional networks of crosslinked polymers that can retain large amounts of water. Hydrogels can provide a stable and tunable matrix for CDs, enhancing their fluorescence, stability, and functionality. CDs@hydrogels, known for their ease of synthesis, strong binding capabilities, and rich surface functional groups, have emerged as promising composite materials. In this review, recent advances in the synthesis and characterization of CDs@hydrogels, composite materials composed of CDs and various types of natural or synthetic hydrogels, are summarized. The potential applications of CDs@hydrogels in fluorescence sensing, adsorption, drug delivery, antibacterial activity, flexible electronics, and energy storage are also highlighted. The current challenges and future prospects of CDs@hydrogels systems for the novel functional materials are discussed.

Syringeable Near-Infrared Light-Activated In Situ Immunogenic Hydrogel Boosts the Cancer-Immunity Cycle to Enhance Anticancer Immunity.

Effective anticancer immunity depends on properly activating multiple stepwise events in the cancer-immunity cycle. An immunologically "cold" tumor microenvironment (TME) engenders immune evasion and refractoriness to conventional checkpoint blockade immunotherapy. Here, we combine nanoparticle formulations and an in situ formed hydrogel scaffold to treat accessible tumors locally and to stimulate systemic immunity against metastatic tumor lesions. The nanoparticles encapsulate poly(ε-caprolactone)-derived cytotoxic chemotherapy and adjuvant of Toll-like receptor 7/8 through a reactive oxygen species (ROS)-cleavable linker that can be self-activated by the coassembled neighboring photosensitizer following near-infrared (NIR) laser irradiation. Further development results in syringeable, NIR light-responsive, and immunogenic hydrogel (iGEL) that can be implanted peritumorally and deposited into the tumor surgical bed. Upon NIR laser irradiation, the generated ROS induces iGEL degradation and bond cleavage in the polymer-drug conjugates, triggering the immunogenic cell death cascade in cancer cells and spontaneously releasing encapsulated agents to rewire the cancer-immunity cycle. Notably, upon application in multiple preclinical models of melanoma and triple-negative breast cancer, which are aggressive and refractory to conventional immunotherapy, iGEL induces durable remission of established tumors, extends postsurgical tumor-free survival, and inhibits metastatic burden. The result of this study is a locally administrable immunogenic hydrogel for triggering host systemic immunity to improve immunotherapeutic efficacy with minimal off-target side effects.

Sophocarpine attenuates doxorubicin-induced heart injury through inhibition of fibrosis.

BACKGROUND: Doxorubicin (DOX) is a potent anti-cancer medication that is associated with numerous adverse effects, particularly concerning damage to the heart. METHODS: This study aimed to investigate the impact of sophocarpine (SOP) on DOX-induced heart injury through both in vivo and in vitro experiments. The experimental techniques employed encompassed echocardiography, hematoxylin/eosin (H&E) staining, Masson staining, immunohistochemical staining, western blotting, and so on. RESULTS: Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements in both left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase-MB and lactate dehydrogenase, while SOP decreased these indices. Staining methods such as H&E and Masson showed that SOP reversed the pathological changes induced by DOX. DOX elevated the expression levels of fibrosis-associated proteins such as Collagen I, Collagen III, α-SMA, Fibronectin, MMP-2, and MMP-9. However, SOP reversed these changes. Moreover, the study further revealed that SOP inhibited the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: These findings imply that SOP has the potential to mitigate DOX-induced heart injury by suppressing fibrosis. The underlying molecular mechanism may involve the inhibition of the TGF-ß1/Smad3 signaling pathway.

Promising Cytokine Adjuvants for Enhancing Tuberculosis Vaccine Immunity.

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), remains a formidable global health challenge, affecting a substantial portion of the world's population. The current tuberculosis vaccine, bacille Calmette-Guérin (BCG), offers limited protection against pulmonary tuberculosis in adults, underscoring the critical need for innovative vaccination strategies. Cytokines are pivotal in modulating immune responses and have been explored as potential adjuvants to enhance vaccine efficacy. The strategic inclusion of cytokines as adjuvants in tuberculosis vaccines holds significant promise for augmenting vaccine-induced immune responses and strengthening protection against M. tuberculosis. This review delves into promising cytokines, such as Type I interferons (IFNs), Type II IFN, interleukins such as IL-2, IL-7, IL-15, IL-12, and IL-21, alongside the use of a granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant, which has shown effectiveness in boosting immune responses and enhancing vaccine efficacy in tuberculosis models.

Prognostic Factors of Pediatric Acute Myeloid Leukemia Patients with t(8;21) (q22;q22): A Single-Center Retrospective Study.

This retrospective study aimed to analyze the treatment effect and prognostic factors of pediatric acute myeloid leukemia (AML) patients with t(8;21). A total of 268 newly diagnosed pediatric AML (pAML) enrolled from 1 January 2005 to 31 December 2022 were retrospectively reviewed, and 50 (18.7%) patients harbored t(8;21) translocation. CR rate, OS, EFS, and RFS were assessed by multivariate Logistic and Cox regression models in these patients. Of the 50 patients, 2 patients abandoned treatment during the first induction course. Of the remaining 48 patients who received double-induction therapy and were included in the final analyses, CR1 and CR2 were 75.0% (36/48) and 95.8% (46/48), respectively. The overall three-year OS, EFS, and RFS were 68.4% (95% CI, 55.0-85.1), 64.2% (95% CI, 50.7-81.4), and 65.5% (95% CI, 51.9-82.8), respectively. The presence of loss of sex chromosome (LOS) at diagnosis (n = 21) was associated with a better 3-year OS [87.5% (95% CI, 72.7-100) vs. 52.7% (95% CI, 35.1-79.3), p = 0.0089], 3-year EFS [81.6% (95% CI, 64.7-100) vs. 49.7% (95% CI, 32.4-76.4), p = 0.023], and 3-year RFS [81.6% (95% CI, 64.7-100) vs. 51.7% (95% CI, 33.9-78.9), p = 0.036] than those without LOS (n = 27), and it was also an independent good prognostic factor of OS (HR, 0.08 [95% CI, 0.01-0.48], p = 0.005), EFS (HR, 0.22 [95% CI, 0.05-0.85], p = 0.029), and RFS (HR, 0.21 [95% CI, 0.05-0.90], p = 0.035). However, extramedullary leukemia (EML) featured the independent risk factors of inferior OS (HR, 10.99 [95% CI, 2.08-58.12], p = 0.005), EFS (HR, 4.75 [95% CI, 1.10-20.61], p = 0.037), and RFS (HR, 6.55 [95% CI, 1.40-30.63], p = 0.017) in pediatric individuals with t(8;21) AML. Further analysis of combining LOS with EML indicated that the EML+LOS- subgroup had significantly inferior OS (92.9%, [95% CI, 80.3-100]), EFS (86.2%, [95% CI, 70.0-100]), and RFS (86.2%, [95% CI, 80.3-100]) compared to the other three subgroups (all p < 0.001). LOS and EML are independent prognostic factors of OS, EFS, and RFS with t(8;21) pAML patients. LOS combined with EML may help improve risk stratification.

Visible-light-induced three-component reactions of α-diazoesters, quinazolinones and cyclic ethers toward quinazoline-based hybrids.

An effective approach for the construction of 4-short-chain ether attached carbonyl group-substituted quinazolines was developed. Visible-light-induced three-component reactions of α-diazoesters, quinazolinones, and cyclic ethers, with a broad substrate scope and excellent functional group tolerance, under extremely mild conditions without the need for any additional additives and catalysts, selectively led to quinazoline-based hybrids in good to excellent yields. The synthesized hybrids, which are a conglomeration of a quinazoline, a short-chain ether, and a carbonyl group in one molecular skeleton, have potential for application in the development of new drugs or drug candidates.

Targeting the dendritic cell-secreted immunoregulatory cytokine CCL22 alleviates radioresistance.

PURPOSE: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after radiation. EXPERIMENTAL DESIGN: Transcriptomics and high dimensional flow cytometry revealed changes in murine tumor cDC that not only mediate Treg infiltration after RT, but associate with worse survival in human cancer datasets. Antibodies perturbing a cDC-CCL22-Treg axis were tested in syngeneic murine tumors. A prototype interferon-anti-epidermal growth factor receptor fusion protein (αEGFR-IFNα) was examined to block Treg infiltration and promote a CD8+ T cell response after RT. RESULTS: Radiation expands a population of mature cDC1 enriched in immunoregulatory markers that mediates Treg infiltration via the Treg-recruiting chemokine CCL22. Blocking CCL22 or Treg depletion both enhanced RT efficacy. αEGFR-IFNα blocked cDC1 CCL22 production while simultaneously inducing an antitumor CD8+ T cell response to enhance RT efficacy in multiple EGFR-expressing murine tumor models, including following systemic administration. CONCLUSIONS: We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

Dihydroquercetin regulates HIF-1α/AKT/NR2B signalling to improve impaired brain function in rats with metabolic syndrome.

Dihydroquercetin (DHQ) is commonly used as a dietary additive, but its activity in improving brain injury with metabolic syndrome (MS) remains known. In present study, the MS rat model was induced using 10 % fructose water. The apoptosis rate of primary brain cells was detected. The HIF-1α/AKT/NR2B signalling pathway, levels of KEAP1/NRF2, HO-1 and NQO-1 were detected. In vitro experiments were performed using H2O2-stimulated PC-12 cells. The effect of DHQ on rates of cell survival and apoptosis were detected. After silencing HIF-1α, we further elucidate the mechanism of action of DHQ. The results indicated that DHQ reduced the hyperactivity and inhibited oxidative stress via increasing the levels of HIF-1α/AKT/NR2B signalling pathway, whereas regulated KEAP1/NRF2 pathway. In vitro experiments showed that the HIF-1α plays an important role in this process. Overall, DHQ may improve impaired brain function in rats with metabolic syndrome by regulating the HIF-1α/AKT/NR2B signalling pathway.

Neural correlates of emotion-label vs. emotion-laden word processing in late bilinguals: evidence from an ERP study.

The brain processes underlying the distinction between emotion-label words (e.g. happy, sad) and emotion-laden words (e.g. successful, failed) remain inconclusive in bilingualism research. The present study aims to directly compare the processing of these two types of emotion words in both the first language (L1) and second language (L2) by recording event-related potentials (ERP) from late Chinese-English bilinguals during a lexical decision task. The results revealed that in the early word processing stages, the N170 emotion effect emerged only for L1 negative emotion-laden words and L2 negative emotion-label words. In addition, larger early posterior negativity (EPN) was elicited by emotion-laden words than emotion-label words in both L1 and L2. In the later processing stages, the N400 emotion effect was evident for L1 emotion words, excluding positive emotion-laden words, while it was absent in L2. Notably, L1 emotion words elicited enhanced N400 and attenuated late positive complex (LPC) compared to those in L2. Taken together, these findings confirmed the engagement of emotion, and highlighted the modulation of emotion word type and valence on word processing in both early and late processing stages. Different neural mechanisms between L1 and L2 in processing written emotion words were elucidated.

Negation and social avoidance in language recruits the right inferior frontal gyrus: a tDCS study.

Introduction: In the process of comprehension, linguistic negation induces inhibition of negated scenarios. Numerous studies have highlighted the role of the right Inferior Frontal Gyrus (rIFG) - a key component of the inhibitory network - in negation processing. Social avoidance can be linguistically portrayed using attitudinal verbs such as "exclude" vs. "include", which inherently carry negative connotations. Consequently, we hypothesize that the interplay between explicit negation and the implicit negativity of avoidance verbs can be modulated via transcranial direct current stimulation (tDCS) targeting the rIFG. Methods: In our study, sixty-four participants read approach/avoidance sentences, which were either affirmative or negative, such as "Anne included (did not include) meat in her diet" vs. "Anne excluded (did not exclude) meat in her diet". This reading task followed a 20-minute tDCS session. The sentences were sequentially displayed, and at 1500 ms post-sentence, a verb was shown - either the one previously mentioned or its semantic alternative counterpart (e.g., included vs. excluded). Results: Findings revealed that anodal stimulation intensifies the inhibitory impact of negation during sentence comprehension. Under anodal conditions, negative sentences led to extended reading times for the mentioned verbs compared to their affirmative counterparts, suggesting an increased inhibitory effect on the verb. Furthermore, in avoidance sentences, anodal stimulation resulted in reduced reading times for alternative verbs (e.g. "included") in negative sentences compared to alternative verbs (e.g. "excluded") in negated approach sentences. Discussion: As "avoidance" is semantically equivalent to "non-approach", the inhibitory effect of negation is primarily applied to the implicit negation: NOT EXCLUDED = NOT→NOT (INCLUDED), which consequently activates the representation of the alternative verb making it more available. We further discuss these findings in light of the rIFG's pivotal role in processing attitudinal verbs and linguistic negation. This discussion is framed within the overarching context of the two-step model of negation processing, highlighting its significance in the realm of social communication.

Patient-Controlled Subcutaneous Analgesia with Hydromorphone versus Oral Oxycontin for Opioid Titration of Cancer Pain: A Prospective Multicenter Randomized Trial.

Background: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain. Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5-11.5] hours vs.16.0 [95% CI:11.5-22.5] hours; p<0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0-3.5) than in the oxycontin group.(3.0; 2.5-4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5-3.0) vs 4.5;3.0-6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32). Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p<0.001), without significantly increasing adverse events (p=0.32).

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

TeamSTEPPS improves patient safety.

BACKGROUND: Examine how Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) can be used to manage patient safety and improve the standard of care for patients. METHODS: In order to improve key medical training in areas like surgical safety management, blood transfusion closed-loop management, drug safety management and identity recognition, we apply the TeamSTEPPS teaching methodology. We then examine the effects of this implementation on changes in pertinent indicators. RESULTS: Our hospital's perioperative death rate dropped to 0.019%, unscheduled reoperations dropped to 0.11%, and defined daily doses fell to 24.85. Antibiotic usage among hospitalised patients declined to 40.59%, while the percentage of antibacterial medicine prescriptions for outpatient patients decreased to 13.26%. Identity recognition requirements were implemented at a rate of 94.5%, and the low-risk group's death rate dropped to 0.01%. Critical transfusion episodes were less common, with an incidence of 0.01%. The physician's TeamSTEPPS Teamwork Perceptions Questionnaire and Teamwork Attitudes Questionnaire scores dramatically improved following the TeamSTEPPS team instruction course. CONCLUSION: An evidence-based team collaboration training programme called TeamSTEPPS combines clinical practice with team collaboration skills to enhance team performance in the healthcare industry and raise standards for medical quality, safety, and effectiveness.

Localization of G1A1a Allergenic Domain Destroyed by Thermal Processing.

Glycinin is an important allergenic protein. A1a is the acidic chain of the G1 subunit in glycinin (G1A1a), and it has strong allergenicity. In this study, we used phage display technology to express the protein of G1A1a and its overlapping fragments and an indirect enzyme-linked immunosorbent assay (iELISA) to determine the antigenicity and allergenicity of the expressed protein. After three rounds of screening, it was determined that fragment A1a-2-B-I (151SLENQLDQMPRRFYLAGNQEQEFLKYQQEQG181) is the allergenic domain of G1A1a destroyed by thermal processing. In addition, three overlapping peptides were synthesized from fragments A1a-2-B-I, and a linear epitope was found in this domain through methods including dot blot and iELISA. Peptide 2 (157DQMPRRFYLANGNQE170) showed allergenicity, and after replacing it with alanine, it was found that amino acids D157, Q158, M159, and Y164 were the key amino acids that affected its antigenicity, while Q158, M159, R162, and N168 affected allergenicity.

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis.

Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L-arginine-induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up-regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D-lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C-reactive protein. Inhibition of Pck1 by 3-Mercaptopicolinic acid hydrochloride (3-MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3-MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D-lactate, endotoxin, and FITC-Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3-MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3-MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.

Cryo-EM structure of human HCN3 channel and its regulation by cAMP.

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Nutritional support therapy for liver transplantation in an adult-onset type II citrullinemia patient: a case report.

Liver transplantation is an effective measure to treat adult-onset type II citrullinemia (CTLN2). Active and effective perioperative nutrition support is a very important treatment for the prognosis of such patients. In this paper, we analyzed the process, results, and outcome of nutritional support therapy in a case of CTLN2, and concluded that the perioperative nutritional support program for CTLN2 patients should be followed prior to surgery:1.because of the prevalence of severe malnutrition in CTLN2 patients, Enteral nutrition (EN) combined with Parenteral nutrition (PN) should be the first choice for nutritional support; 2. daily energy intake should be 35 ~ 40 kcal/kg; 3. the nutritional formula should be composed of low-carbohydrates and high medium-chain triglyceride (MCT). Postoperative: initiating EN as soon as possible is recommended to restore intestinal function and adjuvant PN might be taken into consideration in the early stage. The purpose of this case was to provide experience for the development and adjustment of the perioperative nutritional support regimen for CTLN2 patients.

Tandem Mass Tag-Based Proteomic Analysis of Normal and Degenerated Human Intervertebral Discs.

Background: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear. Methods: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography-tandem mass spectrometry (LC‒MSMS/MS). Results: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD. Conclusion: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.

Nanoparticle-assisted Targeting Delivery Technologies for Preventing Organ Rejection.

Although organ transplantation is a life-saving medical procedure, the challenge of posttransplant rejection necessitates safe and effective immune modulation strategies. Nanodelivery approaches may have the potential to overcome the limitations of small-molecule immunosuppressive drugs, achieving efficacious treatment options for transplant tolerance without compromising overall host immunity. This review highlights recent advances in biomaterial-assisted formulations and technologies for targeted nanodrug delivery with transplant organ- or immune cell-level precision for treating graft rejection after transplantation. We provide an overview of the mechanism of transplantation rejection, current clinically approved immunosuppressive drugs, and their relevant limitations. Finally, we discuss the targeting principles and advantages of organ- and immune cell-specific delivery technologies. The development of biomaterial-assisted novel therapeutic strategies holds considerable promise for treating organ rejection and clinical translation.