Tumor-associated macrophage-derived itaconic acid contributes to nasopharyngeal carcinoma progression by promoting immune escape via TET2.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.

Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway.

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Taurine protects against myelin damage of sciatic nerve in diabetic peripheral neuropathy rats by controlling apoptosis of schwann cells via NGF/Akt/GSK3ß pathway.

Diabetic peripheral neuropathy is a common complications of Type 2 Diabetes and its main pathological feature is myelin sheath damage of peripheral nerve that was induced by Schwann cells (SCs) apoptosis. Increasing evidence suggested that taurine might play a role in improving DPN because of its ability to prevent SCs apoptosis. In this study, we explore the effect of taurine on preventing SCs apoptosis and its underlying mechanism. Sprague Dawley rats were treated with streptozotocin to establish the diabetes model. Rats were randomly divided into control, diabetes, taurine treatment (as giving 0.5%, 1% and 2% taurine in drinking water) groups. RSC96 cell (a rat SCs line) was used for intervention experiments in vitro. Results showed that taurine significantly corrected morphology of damaged myelin sheath and inhibited SCs apoptosis in sciatic nerve of diabetic rats. Moreover, taurine prevented apoptosis of RSC96 cells exposed to high glucose. Mechanistically, taurine up-regulated NGF expression and phosphorylation levels of Akt and GSK3ß, while, blocking activation of NGF and phosphorylation of Akt and GSK3ß increased apoptosis of high glucose-exposed RSC96 cells with taurine supplement. These results revealed taurine improved the myelin sheath damage of sciatic nerve in diabetic rats by controlling SCs apoptosis via NGF/Akt/GSK3ß signaling pathways, which provides some clues that taurine might be effective and feasible candidate for the treatment of DPN.

Anti-apoptotic Effect of Taurine on Schwann Cells Exposed to High Glucose In Vitro.

It was reported that apoptosis of Schwann cells could increase in the diabetic rats. The studies showed that taurine inhibited apoptosis in a variety of cells. However, there were few reports on studying the protection of taurine against apoptosis of Schwann cells induced by high glucose (HG) and the underlying mechanism. In our study, the cells were divided into five groups: Control: the normal medium; HG group: 50 mM high glucose; T1: 50 mM high glucose+Taurine (10 mM) group; T2: 50 mM high glucose+Taurine (20 mM) group; T3: 50 mM high glucose+Taurine (40 mM) group. We used MTT and Tunel assays to measure the cell viability and apoptosis, respectively. Then, we also used western blotting to detect the protein levels of apoptosis-related protein. The results demonstrate that taurine promoted cell viability and decreased apoptosis in RSC96 cells exposed to HG. Furthermore, taurine markedly improved imbalance of Bax and Bcl-2, inhibited the translocation of Cytochrome C (Cyt C) from mitochondria to cytosol and reduced caspase-3 activity in HG-induced RSC96 cells. Our results indicate that taurine protect against apoptosis of Schwann cells induced by HG via inhibiting mitochondria-dependent caspase-3 pathway.

Protective Effect of Taurine on Apoptosis of Spinal Cord Cells in Diabetic Neuropathy Rats.

Diabetes mellitus (DM) is a condition characterized by chronic hyperglycemia, which leads to diabetic neuropathy and apoptosis in the spinal cord. Taurine has been found to ameliorate the diabetic neuropathy and control apoptosis in various tissues. However, there are few reports that discuss the direct relationship between spinal cord and anti-apoptotic effect of taurine. In this study, DM was induced in male SD rats with STZ @ 25 mg/Kg of body weight in combination with high fat diet. After 2 weeks, they were divided into four groups as DM: diabetic rats, T1 (0.5%), T2 (1%) and T3 (2%) taurine solution, while control group was non-diabetic rats (no treatment). The results showed that DM increased apoptosis, decreased phosphorylated Akt and Bad. DM decreased expression of Bcl-2 and increased the Bax. Moreover, the release of cytochrome c into cytosol was increased in DM and activation of caspase-3 was also increased. However, taurine reversed all these abnormal changes in a dose dependent manner. Our results suggested the involvement of Akt/Bad signaling pathway and mitochondrial apoptosis pathway in protective effect of taurine against apoptosis in the spinal cord of diabetic rats. Therefore, taurine may be a potential medicine against diabetic neuropathy by controlling apoptosis.

Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Diabetes causes memory loss. Hippocampus is responsible for memory and increased apoptosis was found in diabetes patients. Taurine improved memory in diabetes condition. However, mechanism is unclear. In current study, hippocampal cell line HT-22 cells were subjected to analysis as five groups i.e. Control, High glucose (HG) at concentration of 150 mM, HG + 10 mM (T1), 20 mM (T2) and 40 mM (T3) taurine solution. TUNEL assay showed that HG increased the number of apoptotic cell significantly while taurine reduced apoptosis. Taurine increased phosphorylation of Akt in HT-22 cell treated with HG, and increased phosphorylation of Bad (p-Bad) was seen suggesting involvement of Akt/Bad signaling pathway. Expression of Bcl-2 was reduced in HG group but taurine improved this. Bax expression showed opposite trend. This indicated that taurine may reduce apoptosis by controlling balance of Bcl-2 and Bax. When the activation of Akt was blocked by using of perifosine, the effect of taurine disappears either partially or altogether. Thus, it was clear that taurine reduces apoptosis via Akt/Bad pathway in HT-22 cells exposed to HG which further improves downstream balance of Bcl-2 and Bax. This mechanism may be involved in apoptosis of hippocampus cells in diabetic condition.

Taurine Promotes Neuritic Growth of Dorsal Root Ganglion Cells Exposed to High Glucose in Vitro.

Diabetic neuropathy (DN) is the most common chronic complication of DM and its major pathological changes show axonal dysfunction, atrophy and loss. However, there are few reports that taurine promotes neurite growth of dorsal root ganglion (DRG) cells. In current study, DRG neurons were exposed to high glucose (HG) with or without taurine. The neurite outgrowth of DRG neurons was observed by fluorescent immunohistochemistry method. Expression of Gap-43, Akt, phosphorylated Akt, mTOR and phosphorylated mTOR was determined by Western blot assay. Our results showed that HG significantly decreased the neurite outgrowth and expression of Gap-43 in DRG neurons. Moreover, phosphorylated levels of Akt and mTOR were downregulated in DRG neurons exposed to HG. On the contrary, taurine supplementation significantly reversed the decreased neurite outgrowth and Gap-43 expression, and the downregulated phosphorylated levels of Akt and mTOR. However, the protective effects of taurine were blocked in the presence of PI3K antagonists LY294002 or Akt antagonists Perifosine. These results indicate that taurine promotes neurite outgrowth of DRG neurons exposed to HG via activating Akt/mTOR signal pathway.

The microRNAs Expression Profile in Sciatic Nerves of Diabetic Neuropathy Rats After Taurine Treatment by Sequencing.

Taurine protect against diabetic neuropathy. However, the protective mechanism of taurine has been poorly understood. It has been demonstrated that microRNAs (miRNAs) are involved in regulating gene expression. Therefore, it is interested in whether taurine affects miRNAs expression profile in peripheral nerve tissue of diabetic neuropathy. In the present study, rats were treated as three group: (1) control (Con) group, (2) diabetic mellitus (DM) group and (3) taurine treatment (Tau) group. Sciatic nerve tissue was harvested and miRNA expression was determined using sequencing. The results showed that 80 miRNAs showed significant difference in DM group compared to Con group, of which 20 miRNAs showed up-regulating, as well as, 60 miRNAs showed down-regulating. On the other hand, 215 differential miRNAs were found between DM and Tau groups. Moreover, the numbers of up-regulated and down-regulated miRNAs were 1 and 214, respectively. Twelve specific miRNAs were screened out and the target genes were obtained by target analysis software. GO and KEGG enrichment analyses showed that these potential target genes for the miRNAs might be involved in axon guidance, generation of neurons, nervous system development and neurogenesis. Our results provided a miRNA profile for further exploring protective mechanisms of taurine against diabetic peripheral neuropathy.

Correction to: Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.

Ameliorative effects of taurine against diabetes: a review.

Diets in rats and humans have shown promising results. Taurine improved glucagon activity, promoted glycemic stability, modified glucose levels, successfully addressed hyperglycemia via advanced glycation end-product control, improved insulin secretion and had a beneficial effect on insulin resistance. Taurine treatment performed well against oxidative stress in brain, increased the secretion of required hormones and protected against neuropathy, retinopathy and nephropathy in diabetes compared with the control. Taurine has been observed to be effective in treatments against diabetic hepatotoxicity, vascular problems and heart injury in diabetes. Taurine was shown to be effective against oxidative stress. The mechanism of action of taurine cannot be explained by one pathway, as it has many effects. Several of the pathways are the advanced glycation end-product pathway, PI3-kinase/AKT pathway and mitochondrial apoptosis pathway. The worldwide threat of diabetes underscores the urgent need for novel therapeutic measures against this disorder. Taurine (2-aminoethane sulfonic acid) is a natural compound that has been studied in diabetes and diabetes-induced complications.

[Using an Information System to Optimize the ACLS Process at the Emergency Department].

The best first-aid treatment for cardiac arrest patients is advanced cardiac life support (ACLS) in terms both of saving lives and of reducing the incidence of sequelae. The American Heart Association (AHA) published updated ACLS guidelines for care in 2015. These updated guidelines emphasized the importance of teamwork in resuscitation, noting that, in addition to standard procedures, team members should be familiar with their distinct roles and should cooperate together during emergent situations. Implementing ACLS is not easy due to stress and unfamiliarity with the process and thus often achieves less-than-optimal results in practice. However, ACLS is a standard approach that uses the same procedures to address different cardiac arrest situations. Therefore, we wanted to use an information system to assist the medical team to fully implement the ACLS process. The information system helps the medical team perform resuscitation actions more intensively and precisely while avoiding problems and mistakes due to forgetfulness / unfamiliarity, facilitating an optimal resuscitation effort. Concurrently, electronic medical and nursing records are completed automatically, avoiding the need for medical staff to compile these records afterwards. This information system helps save time and effort and improves precision. Furthermore, data analysis is more convenient, which facilitates the effective management and supervision of resuscitation quality. The information system performs timing, prompting, and guidance in accordance with the ACLS process and records the procedures that will used in emergency treatment (i.e., chest compression frequency, establishment of intravenous route, placement of endotracheal tubes, electric shock, drug type, dose) with a simple click of a mouse. Finally, the associated medical record is completed and logged as soon as the automatically generated file is uploaded. All hospital staffs may use this information system to assist in the implementation of advanced CPR. The system improves the quality of the first aid measures applied in life support, reduces the burden on clinics and medical staff, and streamlines the preparation and submission of medical records.

Sedative and hypnotic effect of freeze-dried paeoniflorin and sini san freeze-dried powder in pentobarbital sodium-induced mice.

OBJECTIVE: To investigate the sedative and hypnotic activity of paeoniflorin and freeze-dried Sini San powder on mice and provide a reliable method for determining the pharmacodynamic material basis of Sini San. METHODS: Male adult mice weighing 20-22 g were used in this study. Three experiments were carried out. Synergism with pentobarbital was used as an index for hypnotic effect. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were recorded in each experiment. RESULTS: The coefficient of variation of the suprathreshold dose (55 mg/kg) was significantly lower than that of the threshold dose. The sleep latency of mice was significantly decreased, and the sleeping time of mice was significantly prolonged. The effects of paeoniflorin and Sini San on prolonging the sleeping time of mice induced by pentobarbital sodium were significantly stronger than those in the control group. CONCLUSION: Paeoniflorin produces significant sedative and hypnotic effects, and there is an obvious dose-effect relationship.

Optimal image quality and radiation doses with optimal tube voltages/currents for pediatric anthropomorphic phantom brains.

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.

Management of post-radiation carotid blowout syndrome in patients with head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: Carotid blowout syndrome (CBS) is a rare but potentially life-threatening complication that can occur in patients with head and neck cancer (HNC), especially with a history of radiotherapy. This study aimed to review and initially compare managements for post-radiation CBS in patients with HNC. MATERIALS AND METHODS: A systematic review of published studies was performed. Information including management, survival, and complication were collected. RESULTS: A total of 39 articles and 917 cases were included in the systematic review. The interval between radiation therapy and CBS ranged from 1.2 years to 17.8 years. The managements of CBS included embolization, stent, bypass surgery, surgical ligation, electrocoagulation, flap coverage, arterial repair, and nasopharyngeal packing. The cumulative 30-day, 1-year, and 2-year overall survival rates were 85.2 %, 48.9 %, and 37.0 %, respectively, with a median survival time of 11.3 months. Disease progression and rebleeding were the most common death causes. The lowest rebleeding rate and neurologic complications rate were presented in cases receiving bypass surgery at 1.4 % and 10.8 %, respectively. The highest rebleeding rate of 35.6 % was showed in cases underwent stent, and the highest neurologic complications rate of 32.0 % was showed in cases underwent ligation. CONCLUSION: Post-radiation CBS in patients with HNC had a low survival rate and high complication rate. Rebleeding and neurologic complication were common complications. Endovascular embolization and stent were the mainstream management, and bypass surgery presented a promising outcome in survival and complication for selected patients.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

Artificial intelligence facilitates measuring reflux episodes and postreflux swallow-induced peristaltic wave index from impedance-pH studies in patients with reflux disease.

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.

Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction.

Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.

Construction of the prognostic signature of alternative splicing revealed the prognostic predictor and immune microenvironment in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSC) is a prevalent and heterogeneous malignancy with poor prognosis and high mortality rates. There is significant evidence of alternative splicing (AS) contributing to tumor development, suggesting its potential in predicting prognosis and therapeutic efficacy. This study aims to establish an AS-based prognostic signature in HNSC patients. Methods: The expression profiles and clinical information of 486 HNSC patients were downloaded from the TCGA database, and the AS data were downloaded from the TCGA SpliceSeq database. The survival-associated AS events were identified by conducting a Cox regression analysis and utilized to develop a prognostic signature by fitting into a LASSO-regularized Cox regression model. Survival analysis, univariate and multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the signature and an independent cohort was used for validation. The immune cell function and infiltration were analyzed by CIBERSORT and the ssGSEA algorithm. Results: Univariate Cox regression analysis identified 2726 survival-associated AS events from 1714 genes. The correlation network reported DDX39B, PRPF39, and ARGLU1 as key splicing factors (SF) regulating these AS events. Eight survival-associated AS events were selected and validated by LASSO regression to develop a prognostic signature. It was confirmed that this signature could predict HNSC outcomes independent of other variables via multivariate Cox regression analysis. The risk score AUC was more than 0.75 for 3 years, highlighting the signature's prediction capability. Immune infiltration analysis reported different immune cell distributions between the two risk groups. The immune cell content was higher in the high-risk group than in the low-risk group. The correlation analysis revealed a significant correlation between risk score, immune cell subsets, and immune checkpoint expression. Conclusion: The prognostic signature developed from survival-associated AS events could predict the prognosis of HNSC patients and their clinical response to immunotherapy. However, this signature requires further research and validation in larger cohort studies.

Effect of deep brain stimulation on brain network and white matter integrity in Parkinson's disease.

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.