A novel approach for estimating lung tumor motion based on dynamic features in 4D-CT.

Due to the high expenses involved, 4D-CT data for certain patients may only include five respiratory phases (0%, 20%, 40%, 60%, and 80%). This limitation can affect the subsequent planning of radiotherapy due to the absence of lung tumor information for the remaining five respiratory phases (10%, 30%, 50%, 70%, and 90%). This study aims to develop an interpolation method that can automatically derive tumor boundary contours for the five omitted phases using the available 5-phase 4D-CT data. The dynamic mode decomposition (DMD) method is a data-driven and model-free technique that can extract dynamic information from high-dimensional data. It enables the reconstruction of long-term dynamic patterns using only a limited number of time snapshots. The quasi-periodic motion of a deformable lung tumor caused by respiratory motion makes it suitable for treatment using DMD. The direct application of the DMD method to analyze the respiratory motion of the tumor is impractical because the tumor is three-dimensional and spans multiple CT slices. To predict the respiratory movement of lung tumors, a method called uniform angular interval (UAI) sampling was developed to generate snapshot vectors of equal length, which are suitable for DMD analysis. The effectiveness of this approach was confirmed by applying the UAI-DMD method to the 4D-CT data of ten patients with lung cancer. The results indicate that the UAI-DMD method effectively approximates the lung tumor's deformable boundary surface and nonlinear motion trajectories. The estimated tumor centroid is within 2 mm of the manually delineated centroid, a smaller margin of error compared to the traditional BSpline interpolation method, which has a margin of 3 mm. This methodology has the potential to be extended to reconstruct the 20-phase respiratory movement of a lung tumor based on dynamic features from 10-phase 4D-CT data, thereby enabling more accurate estimation of the planned target volume (PTV).

Shared and distinct prefrontal cortex alterations of implicit emotion regulation in depression and anxiety: An fNIRS investigation.

BACKGROUND: Emotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders. METHODS: We investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments. RESULTS: We found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients. LIMITATIONS: fNIRS has limited depth and spatial resolution. CONCLUSION: Our fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches.

Inactivity May Identify Older Intensive Care Unit Survivors at Risk for Post-Intensive Care Syndrome.

BACKGROUND: Older adults (≥age 65) admitted to an intensive care unit (ICU) are profoundly inactive during hospitalization. Older ICU survivors often experience life-changing symptoms, including cognitive dysfunction, physical impairment, and/or psychological distress, which are components of post-intensive care syndrome (PICS). OBJECTIVES: To explore trends between inactivity and symptoms of PICS in older ICU survivors. METHODS: This study was a secondary analysis of pooled data obtained from 2 primary, prospective, cross-sectional studies of older ICU survivors. After ICU discharge, 49 English- and Spanish-speaking participants who were functionally independent before admission and who had received mechanical ventilation while in the ICU were enrolled. Actigraphy was used to measure post-ICU hourly activity counts (12:00 AM to 11:59 PM). Selected instruments from the National Institutes of Health Toolbox and Patient-Reported Outcomes Measurement Information System were used to assess symptoms of PICS: cognitive dysfunction, physical impairment, and psychological distress. RESULTS: Graphs illustrated trends between inactivity and greater symptom severity of PICS: participants who were less active tended to score worse than one standard deviation of the mean on each outcome. Greater daytime activity was concurrently observed with higher performances on cognitive and physical assessments and better scores on psychological measures. CONCLUSIONS: Post-ICU inactivity may identify older ICU survivors who may be at risk for PICS and may guide future research interventions to mitigate symptom burden.

Associations Between Inactivity and Cognitive Function in Older Intensive Care Unit Survivors.

BACKGROUND/INTRODUCTION: Critically ill older adults are profoundly inactive while in the intensive care unit (ICU), and this inactivity persists after discharge from the ICU. Older ICU survivors who were mechanically ventilated are at high risk for post-ICU cognitive impairment. OBJECTIVES/AIMS: The present study examined the relationship between the ratio of daytime to nighttime activity and executive function in older ICU survivors. METHODS: This was a secondary analysis of pooled data from 2 primary studies of older adults who were functionally independent prior to hospitalization, mechanically ventilated while in ICU, and within 24 to 48 hours post-ICU discharge. Actigraphy recorded daytime activity (mean activity counts per minute, 6 am to 9:59 pm) and nighttime activity (mean activity counts per minute, 10 pm to 5:59 am). A daytime-to-nighttime activity ratio was calculated by dividing daytime activity by nighttime activity. The NIH Toolbox Dimensional Change Card Sort Test assessed cognitive flexibility (DCCST: fully corrected T score). Multivariate regression examined the association between the daytime-to-nighttime activity ratio and DCCST scores, adjusting for 2 covariates (age in years and NIH Toolbox Grip Strength fully corrected T score). RESULTS: The mean daytime-to-nighttime activity ratio was 2.10 ± 1.17 (interquartile range, 1.42). Ratios for 6 participants (13.6%) were less than 1, revealing higher activity during nighttime hours rather than daytime hours. Higher daytime-to-nighttime ratios were associated with better DCCST scores (ß = .364, P = .005). CONCLUSIONS: The proportion of daytime activity versus nighttime activity was considerably low, indicating severe alterations in the rest/activity cycle. Higher daytime-to-nighttime activity ratios were associated with better executive function scores, suggesting that assessment of daytime activity could identify at-risk older ICU survivors during the early post-ICU transition period. Promotion of daytime activity and nighttime sleep may accelerate recovery and improve cognitive function.

Functional connectivity alterations in the frontoparietal network and sensorimotor network are associated with behavioral heterogeneity in blepharospasm.

Objective: Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. Methods: A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. Results: In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. Conclusion: These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.

Radiomics and deep learning models to differentiate lung adenosquamous carcinoma: A multicenter trial.

Adenosquamous carcinoma (ASC) is frequently misdiagnosed or overlooked in clinical practice due to its dual histological components and potential transformation from either adenocarcinoma (ADC) or squamous cell carcinoma (SCC). Our study aimed to differentiate ASC from ADC and SCC by incorporating features of enhanced CTs and clinical characteristics to build radiomics and deep learning models. The classification models were trained in Xiangya Hospital and validated in two other independent hospitals. The areas under the receiver operating characteristic curves (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to estimate the performance. The optimal three-class classification model achieved a maximum AUC of 0.89 and accuracy of 0.81 in external validation sets, AUC of 0.99 and accuracy of 0.99 in the internal test set. These findings highlight the efficacy of our models in differentiating ASC, providing a non-invasive, timely, and accurate diagnostic approach before and during the treatment.

Skin-Inspired Highly Sensitive Tactile Sensors with Ultrahigh Resolution over a Broad Sensing Range.

Flexible tactile sensors with high sensitivity, a broad pressure detection range, and high resolution are highly desired for the applications of health monitoring, robots, and the human-machine interface. However, it is still challenging to realize a tactile sensor with high sensitivity and resolution over a wide detection range. Herein, to solve the abovementioned problem, we demonstrate a universal route to develop a highly sensitive tactile sensor with high resolution and a wide pressure range. The tactile sensor is composed of two layers of microstructured flexible electrodes with high modulus and conductive cotton fabric with low modulus. By optimizing the sensing films, the fabricated tactile sensor shows a high sensitivity of 8.9 × 104 kPa-1 from 2 Pa to 250 kPa because of the high structural compressibility and stress adaptation of the multilayered composite films. Meanwhile, a fast response speed of 18 ms, an ultrahigh resolution of 100 Pa over 100 kPa, and excellent durability over 20 000 loading/unloading cycles are demonstrated. Moreover, a 6 × 6 tactile sensor array is fabricated and shows promising potential application in electronic skin (e-skin). Therefore, employing multilayered composite films for tactile sensors is a novel strategy to achieve high-performance tactile perception in real-time health monitoring and artificial intelligence.

A multiomics approach-based prediction of radiation pneumonia in lung cancer patients: impact on survival outcome.

PURPOSE: To predict the risk of radiation pneumonitis (RP), a multiomics model was built to stratify lung cancer patients. Our study also investigated the impact of RP on survival. METHODS: This study retrospectively collected 100 RP and 99 matched non-RP lung cancer patients treated with radiotherapy from two independent centres. They were divided into training (n = 175) and validation cohorts (n = 24). The radiomics, dosiomics and clinical features were extracted from planning CT and electronic medical records and were analysed by LASSO Cox regression. A multiomics prediction model was developed by the optimal algorithm. Overall survival (OS) between the RP, non-RP, mild RP, and severe RP groups was analysed by the Kaplan‒Meier method. RESULTS: Sixteen radiomics features, two dosiomics features, and one clinical feature were selected to build the best multiomics model. The optimal performance for predicting RP was the area under the receiver operating characteristic curve (AUC) of the testing set (0.94) and validation set (0.92). The RP patients were divided into mild (≤ 2 grade) and severe (> 2 grade) RP groups. The median OS was 31 months for the non-RP group compared with 49 months for the RP group (HR = 0.53, p = 0.0022). Among the RP subgroup, the median OS was 57 months for the mild RP group and 25 months for the severe RP group (HR = 3.72, p < 0.0001). CONCLUSIONS: The multiomics model contributed to improving the accuracy of RP prediction. Compared with the non-RP patients, the RP patients displayed longer OS, especially the mild RP patients.

[The Effect of Ena/VASP Family on the Expression of GPIb-IX Complex in Human Megakaryoblastic Leukemia Dami Cells].

OBJECTIVE: To explore the effects of Ena/VASP gene family on the expression of glycoprotein (GP) Ib-IX complex in human megakaryoblastic leukemia Dami cells. METHODS: SiRNAs targeting Ena/VASP gene family were designed and synthesized to interfere Enah, EVL and VASP gene expression. When the siRNAs were transfected into Dami cells by using LipofectamineTM 2000 for 48 h, the expression of GPIb-IX complex was detected by quantitative real-time PCR, Western blot and flow cytometry. RESULTS: We successfully established siVASP , siEVL and si Enah Dami cell lines. And it was found that the expression of GPIb-IX complex had no evident reduction in siEVL or siVASP Dami cells at both mRNA and protein level, while the total protein and membrane protein of GPIb-IX complex were obviously reduced when Enah was knocked down. CONCLUSION: Enah could affect the expression of GPIb-IX complex in human megakaryoblastic leukemia Dami cells, but the underlying mechanism still needs to be further explored.

ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway.

The molecular mechanism of tumor metastasis, especially how metastatic tumor cells colonize in a distant site, remains poorly understood. Here we reported that ARHGAP15, a Rho GTPase activating protein, enhanced gastric cancer (GC) metastatic colonization, which was quite different from its reported role as a tumor suppressor gene in other cancers. It was upregulated in metastatic lymph nodes and significantly associated with a poor prognosis. Ectopic expression of ARHGAP15 promoted metastatic colonization of gastric cancer cells in murine lungs and lymph nodes in vivo or protected cells from oxidative-related death in vitro. However, genetic downregulation of ARHGAP15 had the opposite effect. Mechanistically, ARHGAP15 inactivated RAC1 and then decreased intracellular accumulation of reactive oxygen species (ROS), thus enhancing the antioxidant capacity of colonizing tumor cells under oxidative stress. This phenotype could be phenocopied by inhibition of RAC1 or rescued by the introduction of constitutively active RAC1 into cells. Taken together, these findings suggested a novel role of ARHGAP15 in promoting gastric cancer metastasis by quenching ROS through inhibiting RAC1 and its potential value for prognosis estimation and targeted therapy.

Randomized Controlled Study of Self-Managed Music-Guided Exercise Intervention Following Intensive Care.

BACKGROUND: Patients who are discharged from the intensive care unit (ICU; termed ICU survivors) often experience persistent physical impairment. OBJECTIVE: The aim of this study was to explore the effects of a self-managed, music-guided exercise intervention on physical outcomes and adherence rates among ICU survivors. METHODS: A randomized controlled design was used. Following ICU discharge, participants admitted to the ICU for at least 5 days were randomly assigned to a music group ( n = 13) or an active control group ( n = 13). Activity counts were measured using an Actiwatch, and the physical health score was measured using the Patient-Reported Outcomes Measurement Information System global health subscale. Adherence to exercise was documented daily. Independent t -tests were used for data analysis. RESULTS: Data were analyzed for 26 participants. The mean age was 62.8 ± 13.8 years, 53.8% were male, 65.4% were White, and mean Acute Physiology and Chronic Health Evaluation severity of illness score was 59 ± 23.4. Global health physical scores were significantly higher in the music group than in the active control group. Although not significantly different, music group participants tended to be more active and had higher physical activity and adherence rates compared to those in the active control group. CONCLUSION: A self-managed, music-guided exercise intervention demonstrated positive benefits on physical outcomes. Future clinical trials with a larger sample size should be conducted to examine the effects of this tailored, cost-effective, innovative, self-managed exercise intervention among ICU survivors.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Changes in Telomere Length and Indicators of Oxidative Stress in Critically Ill Mechanically Ventilated Adults - A Pilot Study.

BACKGROUND: Telomeres are structures at the end of chromosomes that shorten with each cell division. The purpose of this pilot project is to report changes in telomere length (T/S ratio), indicators of oxidative stress (serum protein carbonyl, vitamin C, GSH:GSSG, and total antioxidant capacity) from Intensive Care Unit (ICU) admission to ICU discharge, and to explore their association with ICU-related morbidities among critically ill mechanically ventilated adults. METHODS: Blood was collected from mechanically ventilated patients (n = 25) at enrollment and within 48 hours of ICU discharge. Telomere length from peripheral blood mononuclear cells (PBMCs) was determined using RTqPCR. ELISAs were used to measure indicators of oxidative stress. Descriptive analysis, paired t-tests, and Pearson's correlations were performed. RESULTS: Mean age was 62.0 ± 12.3 years, 28.6% were male, and 76.2% were White with disease severity using APACHE III (74.6 ± 24.6) and SOFA (7.6 ± 3.2). Mean T/S ratios shortened (ICU: 0.712, post-ICU: 0.683, p < 0.001, n = 19) and serum protein carbonyl increased (ICU: 7437 nmol/mg ± 3328, post-ICU: 10,254 nmol/mg ± 3962, p < 0.005) as did the oxidative stress index (protein carbonyl/GSH:GSSG, ICU: 1049.972 ± 420.923, post-ICU: 1348.971 ± 417.175, p = 0.0104). T/S ratio was positively associated with APACHE III scores (ICU: r = 0.474, post-ICU: r = 0.628, p < 0.05). CONCLUSIONS: Pilot findings suggest that critical illness significantly correlates with telomere attrition, perhaps due to increased oxidative stress. Future larger and longitudinal studies investigating mechanisms of telomere attrition and associations with clinical outcomes are needed to identify potential modifiable factors for subsequent intervention to improve outcomes for critically ill patients.

The Relationship Between Telomeres, Cognition, Mood, and Physical Function: A Systematic Review.

Background and Purpose: Cognitive, affective, and physical symptoms and alterations in their function are seen across chronic illnesses. Data suggest that environmental, psychological, and physiological factors contribute to symptom experience, potentially through loss of telomeres (telomere attrition), structures at the ends of chromosomes. Telomere length is affected by many factors including environmental (e.g., exercise, diet, smoking) and physiological (e.g., response to stress), as well as from oxidative damage and inflammation that occurs in many disease processes. Moreover, telomere attrition is associated with chronic disease (cancer, cardiovascular disease, Alzheimer's disease) and predicts higher morbidity and mortality rates. However, findings are inconsistent among telomere roles and relationships with health outcomes. This article aims to synthesize the current state-of-the-science of telomeres and their relationship with cognitive, affective, and physical function and symptoms. Method: A comprehensive literature search was performed in two databases: CINAHL and PUBMED. A total of 33 articles published between 2000 and 2022 were included in the final analysis. Results: Telomere attrition is associated with various changes in cognitive, affective, and physical function and symptoms. However, findings are inconsistent. Interventional studies (e.g., meditation and exercise) may affect telomere attrition, potentially impacting health outcomes. Conclusion: Nursing research and practice are at the forefront of furthering the understanding of telomeres and their relationships with cognitive, affective, and physical function and symptoms. Future interventions targeting modifiable risk factors may be developed to improve health outcomes across populations.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy.

BACKGROUND: High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions. AIM: To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen. METHODS: Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response. CONCLUSION: Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Single-gene knockout-coupled omics analysis identifies C9orf85 and CXorf38 as two uncharacterized human proteins associated with ZIP8 malfunction.

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers.

Electroacupuncture on Hemifacial Spasm and Temporomandibular Joint Pain Co-Morbidity: A Case Report.

Hemifacial spasm (HFS) and temporomandibular joint (TMJ) pain are common facial diseases which cause depression, anxiety, insomnia, and poor quality of life. However, currently there are still no effective therapies to treat HFS and TMJ. Electroacupuncture (EA) has advantages of safety, rapid work, easy operation and convenience. Here, we reported a case of a 50-year-old woman who presented with irregular spasm of eyelids and facial muscles on the left side, and TMJ pain on the right side. The patient had been treated with carbamazepine (20mg per day) and alternative therapies for a year, but still not much improvement in the symptoms. The scores of the Jankovic Rating Scale (JRS), global rating scale (GRS), and visual analog scale (VAS) were 7, 60, and 7 points, respectively. The EMG test showed that the spastic side had higher R1 amplitude, longer R2 duration, and larger R2 area than the non-spasmodic side, and the occurrence rate of the lateral spread responses (LSR) in the Orbicularis oris and the Orbicularis oculi muscle was 60% and 40%, respectively. We considered this patient had left HFS and right TMJ pain. EA was successfully undertaken for two periods over 30 weeks. After EA, JRS and VAS were reduced sharply, and the symptoms of HFS were stable without recurrence. However, the frequency of the lower eyelid increased gradually during the 6-month follow-up. These findings reveal that EA with the frequency of 2 Hz and intensity of ~ 1-2 mA may be a benefit for alleviating symptoms of HFS and TMJ pain without adverse reaction. The potential mechanisms of EA in HFS and TMJ pain co-morbidity involve brain stem mechanism and DNIC mechanism for distal acupuncture and segmental mechanism for local acupuncture analgesia.

Dietary phillygenin supplementation ameliorates aflatoxin B1-induced oxidative stress, inflammation, and apoptosis in chicken liver.

Aflatoxin B1 (AFB1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB1 in the liver of chickens. Chickens were administered with AFB1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB1-induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI.

M2-phenotype tumour-associated macrophages upregulate the expression of prognostic predictors MMP14 and INHBA in pancreatic cancer.

Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.

Learning curve of uniportal video-assisted thoracoscopic lobectomy: an analysis of the proficiency of 538 cases from a single centre.

OBJECTIVES: Uniportal video-assisted thoracoscopic surgery (UniVATS) is widely used as a minimally invasive thoracic operation. The goal of our study was to analyse the effect of long-term experience with the UniVATS lobectomy on the learning curve. METHODS: The learning curves were quantitatively evaluated by the unadjusted cumulative sum, and they were segmented using joinpoint linear regression analysis. The variables were compared between subgroups using trend analysis, and linear regression analysis was applied to correlate clinical characteristics at different stages of the learning curve with the duration of the operation. RESULTS: The learning curve for the UniVATS lobectomy can be divided into 3 phases of proficiency at ∼200-300 procedures, with a fourth phase as the number of procedures increases. The 1st-52nd, 52nd-156th, 156th-244th and 244th-538th procedures comprised the preliminary learning stage, preliminary proficiency stage, proficiency stage and advanced proficiency stage, respectively. Surgical outcomes and their variability between stages improved with increasing case numbers, with the most significant addition of an auxiliary operating port and conversions. In multivariable analysis, as stages progressed, influences other than surgical experience increased the operative time, with male and extensive pleural adhesions in the preliminary proficiency stage; male and incomplete pulmonary fissures in the proficiency stage; and male, extensive pleural adhesions and incomplete pulmonary fissures in the advanced proficiency stage. CONCLUSIONS: As the number of procedures increases, there may be 4 different proficiency stages in the UniVATS lobectomy learning curve. The surgeon enters the fourth stage at approximately the 244th procedure. Moreover, at stage 4, the perioperative indicators tend to stabilize, and influences other than surgical experience become more significant.