Spontaneous rupture­induced life­threatening mediastinal mixed germ cell tumor: A case report and therapeutic considerations.

Spontaneous rupture and hemorrhage of mediastinal germ cell tumors is a rare occurrence. In the current report, the case of a 20-year-old male patient who was admitted with chest tightness and dyspnea is presented. An urgent chest CT scan revealed a large tumor in the right anterior mediastinum, measuring ~12 cm in diameter, with associated intratumoral hemorrhage. An emergency thoracotomy was performed to excise the lesion, which revealed that the bleeding was caused by a ruptured tumor. Postoperative pathological findings revealed a mediastinal mixed germ cell tumor consisting of four pathological types: Embryonal carcinoma, seminoma, yolk sac tumor and immature teratoma. Postoperatively, the patient showed marked improvement in the symptoms of dyspnea. However, the follow-up outcome was poor, and the patient succumbed 2 months after surgery. To the best of our knowledge, there are no reports of rupture and hemorrhage involving >4 mixed germ cell tumors. In the present report, the experience of the treatment of the patient is summarized, and literature was reviewed to improve clinicians' awareness of the disease.

Treatment of Adhesive Intestinal Obstruction by Nasogastric Tube Under EnhancedRecovery After Surgery: An Efficacy Analysis.

Objective: To explore the application value of enhanced recovery after surgery (ERAS) in the treatment of adhesive intestinal obstruction (AIO) by nasogastric tube (NGT). Methods: Between December 2020 and December 2022, AIO patients who received NGT treatment at The Fourth Hospital of Changsha were selected, including 43 cases receiving ERAS nursing (observation group) and 35 cases receiving routine care (control group). The two groups were compared in terms of postoperative rehabilitation, as well as their psychology, pain, and quality of life which were evaluated using Self-Rating Anxiety/Depression Scale (SAS/SDS), Visual Analogue Scale (VAS), and Short-Form 36 Item Health Survey (SF-36), respectively. During treatment, the adverse reactions were recorded. Results: In the observation group, the abdominal pain and distension relief time, time to first post-treatment flatus and defecation, abdominal circumference reduction 48 hours after admission, bowel sound recovery, first oral food intake, and extubation time were shorter than those of the control group (P < .05), and the SAS and SDS scores were also lower than those of the control group after treatment (P < .05). At 6-24 hours after treatment, the VAS of the observation group was lower than that of the control group, while the SF-36 score was higher (P < .05). Finally, a lower adverse reaction rate was determined in the observation group compared to the control group (P < .05). Conclusions: ERAS care promotes the recovery of AIO patients after NGT treatment, improves their pain and negative emotions, improves their quality of life, and is extremely valuable for clinical application.

The dynamic variation position and predominant quasispecies of hepatitis B virus: Novel predictors of early hepatocarcinoma.

To find the predictors of early HCC based on the dynamic changes of HBV quasispecies, this study utilizing the second-generation sequencing (NGS) and high-order multiplex droplet digital PCR (ddPCR) technology to examine the HBV quasispecies in serum of total 247 subjects recruited from high-incidence area of HCC. In the discovery stage, 15 non-synonymous Single Nucleotide Polymorphisms (SNPs) with higher variant proportion in HCC case group were founded (all P<0.05). Furthermore, the variant proportions in some of these SNPs were observed changing regularly within 5 years before the onset of HCC, and 5 of them located in HBX, 2 in HBS and 2 in HBC. The HBV predominant quasispecies and their consensus sequences were identified by genetic evolution analysis, in which the high HBS and HBC quasispecies heterogeneity were found associated with the forming of multifarious quasispecies clones, and the HBX gene had the highest proportion of predominant quasispecies (46.7 % in HBX vs 12.7 % and 13.8 % in HBS and HBC respectively) with the key variations (G1512A, A1630G, T1753C/G/A, A1762T and G1764A) determined. In the validation stage, we confirmed that the combined double mutations of G1512A+A1630G, A1762T+G1764A, and the combined triple mutations of T1753C/G/A + A1762T+G1764A, all expressed higher in early HCC cases when comparing with control group (all P<0.05). We also demonstrated the advantages of ddPCR using in multi-variations detection in large-sample for early HCC surveillance and screening. So we think that the dynamic of key HBV variation positions and their different combinations determined by quasispecies anlysis in this study can act as the novel predictors of early hepatocarcinoma and suitable to popularize and apply in HCC screening.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Magnetically Manipulated Optoelectronic Hybrid Microrobots for Optically Targeted Non-Genetic Neuromodulation.

Optically controlled neuromodulation is a promising approach for basic research of neural circuits and the clinical treatment of neurological diseases. However, developing a non-invasive and well-controllable system to deliver accurate and effective neural stimulation is challenging. Micro/nanorobots have shown great potential in various biomedical applications because of their precise controllability. Here, a magnetically-manipulated optoelectronic hybrid microrobot (MOHR) is presented for optically targeted non-genetic neuromodulation. By integrating the magnetic component into the metal-insulator-semiconductor junction design, the MOHR has excellent magnetic controllability and optoelectronic properties. The MOHR displays a variety of magnetic manipulation modes that enables precise and efficient navigation in different biofluids. Furthermore, the MOHR could achieve precision neuromodulation at the single-cell level because of its accurate targeting ability. This neuromodulation is achieved by the MOHR's photoelectric response to visible light irradiation, which enhances the excitability of the targeted cells. Finally, it is shown that the well-controllable MOHRs effectively restore neuronal activity in neurons damaged by ß-amyloid, a pathogenic agent of Alzheimer's disease. By coupling precise controllability with efficient optoelectronic properties, the hybrid microrobot system is a promising strategy for targeted on-demand optical neuromodulation.

PdMo nanoflowers for endogenous/exogenous-stimulated nanocatalytic therapy.

The clinical application of reactive oxygen species (ROS)-mediated tumor treatment has been critically limited by inefficient ROS generation. Herein, we rationally synthesized and constructed the three-dimensional PdMo nanoflowers through a one-pot solvothermal reduction method for elaborately regulated peroxidase-like enzymatic activity and glutathione peroxidase-like enzymatic activity, to promote oxidation ROS evolvement and antioxidation glutathione depletion for achieving intensive ROS-mediated tumor therapy. The three-dimensional superstructure composed of two-dimensional nanosheet subunits can solve the issues by avoiding the appearance of tightly stacked crystalline nanostructures. Significantly, Mo is chosen as a second metal to alloy with Pd because of its more chemical valence and negative ionization energy than Pd for improved electron transfer efficiencies and enhanced enzyme-like activities. In addition, the photothermal effect generated by PdMo nanoflowers could also enhance its enzymatic activities. Thus, this work provides a promising paradigm for achieving highly ROS-mediated tumor therapeutic efficacy by regulating the multi-enzymatic activities of Pd-based nanoalloys.

MCPIP-1 knockdown enhances endothelial colony-forming cell angiogenesis via the TFRC/AKT/mTOR signaling pathway in the ischemic penumbra of MCAO mice.

Cerebral ischemia is a serious disease characterized by brain tissue ischemia and hypoxic necrosis caused by the blockage of blood vessels within the central nervous system. Although stem cell therapy is a promising approach for treating ischemic stroke, the inflammatory, oxidative, and hypoxic environment generated by cerebral ischemia greatly reduces the survival and therapeutic effects of transplanted stem cells. Endothelial colony-forming cells (ECFCs) are a class of precursor cells with strong proliferative potential that can migrate and differentiate directly into mature vascular endothelial cells. Consequently, ECFCs can exert significant therapeutic and reparative effects in diseases associated with vascular injury. Monocyte chemoattractant protein-induced protein 1 (MCPIP-1) exerts multiple biological effects; however, no studies have yet reported its role in the angiogenic function of ECFCs. In this study, we performed Proteome Profiler™ Human Angiogenesis Antibody arrays and tandem mass tag protein profiling to investigate the effect of MCPIP-1 on ECFCs. We demonstrated that MCPIP-1 knockdown enhanced the proliferation, migration, and in vivo and in vitro angiogenic capacity of ECFCs by upregulating the transferrin receptor-activated AKT/m-TOR signaling pathway to promote cellular trophic factor secretion. Furthermore, we found that the lateral ventricular transplantation of ECFCs with lentiviral MCPIP-1 knockdown into mice with middle cerebral artery occlusion increased serum vacular endothelial growth factor(VEGF), angiopoietin-1, and HIF-1a levels, enhanced neovascularization and neurogenesis in the ischemic penumbra, reduced the size of cerebral infarcts, and promoted neurological recovery. Together, these findings suggest new avenues for enhancing the therapeutic efficacy of ECFCs.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydroxysafflor yellow A (HSYA) is the principal bioactive compound isolated from the plant Carthamus tinctorius L. and has been reported to exert neuroprotective effects against various neurological diseases, including traumatic brain injury (TBI). However, the specific molecular and cellular mechanisms underlying HSYA-mediated neuroprotection against TBI are unclear. AIM OF THE STUDY: This study explored the effects of HSYA on autophagy and the NLRP3 inflammasome in mice with TBI and the related mechanisms. MATERIALS AND METHODS: Mice were subjected to TBI and treated with or without HSYA. Neurological severity scoring, LDH assays and apoptosis detection were first performed to assess the effects of HSYA in mice with TBI. RNA-seq was then conducted to explore the mechanisms that contributed to HSYA-mediated neuroprotection. ELISA, western blotting, and immunofluorescence were performed to further investigate the mechanisms of neuroinflammation and autophagy. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was applied to determine the connection between autophagy and the NLRP3 inflammasome. RESULTS: HSYA significantly decreased the neurological severity score, serum LDH levels and apoptosis in mice with TBI. A total of 921 differentially expressed genes were identified in the cortices of HSYA-treated mice with TBI and were significantly enriched in the inflammatory response and autophagy. Furthermore, HSYA treatment markedly reduced inflammatory cytokine levels and astrocyte activation. Importantly, HSYA suppressed neuronal NLRP3 inflammasome activation, as indicated by decreased levels of NLRP3, ASC and cleaved caspase-1 and a reduced NLRP3+ neuron number. It increased autophagy and ameliorated autophagic flux dysfunction, as evidenced by increased LC3 II/LC3 I levels and decreased P62 levels. The effects of HSYA on the NLRP3 inflammasome were abolished by 3-MA. Mechanistically, HSYA may enhance autophagy through AMPK/mTOR signalling. CONCLUSION: HSYA enhanced neuronal autophagy by triggering the AMPK/mTOR signalling pathway, leading to inhibition of the NLRP3 inflammasome to improve neurological recovery after TBI.

Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lasts lifelong and causes noticeably higher premature mortality. Although the core symptoms and other behavioral deficits of ASD can persist or be deteriorated from early development to old age, how aging affects the behaviors and brain anatomy in ASD is largely unknown. DOCK4 is an ASD risk gene highly expressed in the hippocampus, and Dock4 knockout (KO) mice display ASD-like behaviors in adulthood (4- to 6-month-old). In this study, we evaluated the behavioral and hippocampal pathological changes of late-middle-aged (15- to 17-month-old) Dock4 male KO mice. Aged Dock4 KO mice continuously showed similar social deficit, elevated anxiety, and disrupted object location memory as observed in the adulthood, when compared to their wild-type (WT) littermates. Notably, Dock4 KO mice displayed an age-related decline of hippocampal dependent spatial memory, showing decreased spatial memory in Barnes maze than their WT littermates at late middle age. Morphological analysis from WT and Dock4 KO littermates revealed that Dock4 deficiency led to decreased mature neurons and oligodendrocytes but increased astrocytes in the hippocampus of late-middle-aged mice. Together, we report that ASD-like behaviors mostly persist into late-middle age in Dock4 KO mice, with specific alterations of spatial memory and hippocampal anatomy by age, thus providing new evidence for understanding age differences in behavioral deficits of ASD.

Proteomic analysis reveals that ACSL4 activation during reflux esophagitis contributes to ferroptosis-mediated esophageal mucosal damage.

Ferroptosis has been shown to be involved in the pathological process of many diseases. However, the function and mechanism of ferroptosis in reflux esophagitis (RE), especially in the esophageal mucosal damage, remains unknown. The purpose of this study was to screen potential therapeutic target genes that mediate RE esophageal mucosal damage and regulate ferroptosis. RE rats were established by our previous protocol and proteomic analysis of esophageal mucosa was performed. In addition, the ferroptosis-related genes were retrieved from the FerrDb database and were cross analyzed with the differential proteins of proteomics to obtain potential therapeutic target genes Acyl-CoA synthetase long-chain family 4 (ACSL4), a key enzyme for ferroptosis. In the present study, we used the ACSL4 inhibitor rosiglitazone (ROSI) and the ferroptosis inhibitor ferrostatin-1 to intervene with RE rats, and evaluate the levels of protein, histological changes, lipid peroxidation levels, iron accumulation and morphological changes in esophageal tissue by HE staining, Western blot, related kit tests, and transmission electron microscope. The results showed that both ferrostatin-1 and ROSI treatment significantly reduced the levels of iron accumulation and lipid peroxidation, and protected against ferroptosis and esophageal tissue injury in RE rats. Through Immunohistochemical staining, 16SrDNA sequencing, Enzyme linked immunosorbent assay (ELISA), Western blot and other tests on the esophagus, gut, spleen and serum of RE rats, we further found that the changes of esophageal and intestinal microbiota and the increase of peripheral blood LPS were the key factors regulating ferroptosis in esophageal epithelial tissue. On the one hand, LPS could increase the expression of ACSL4 in esophageal tissue by up-regulating special protein 1 (Sp1). On the other hand, LPS could increase the secretion of serum ferritin in spleen and the accumulation of iron in esophageal tissue by activating Capase11/GSDMD pyroptosis pathway. Collectively, this study suggests that ACSL4 and ferroptosis are potential therapeutic targets for RE esophageal mucosal damage, and esophageal and gut microecology play a critical role in this process.

Nomogram based on intramuscular adipose tissue content for predicting the prognosis of patients with gallbladder cancer after radical resection.

Background: To investigate the predictive value of intramuscular adipose tissue content (IMAC) on the outcome of gallbladder cancer (GBC) patients after resection, by then develop and evaluate a nomogram to predict the prognosis of GBC patients. Methods: This research incorporated 123 patients with a pathological diagnosis of GBC. Evaluating the prognosis by the Kaplan-Meier method. Independent predictors of overall survival (OS) were screened using multifactorial Cox regression analysis, and a nomogram was constructed from these. Consistency index and calibration curve were used to identify and calibrate the nomogram. The accuracy of the nomogram was assessed by receiver operating characteristic (ROC) curve and decision curve analysis (DCA) was used to assess the net benefit. Results: Patients with high IMAC showed a worse prognosis. A nomogram was constructed to predict OS based on IMAC. The C-index for the nomogram was 0.804. The calibration curve showed well performance of the nomogram. The area under the ROC curve (AUC) for the nomogram at three and five years was 0.839 and 0.785, respectively. A high net benefit was demonstrated by DCA. Conclusions: IMAC was a valid predictor for GBC patients. A nomogram with good performance is constructed to predict the prognosis of GBC patients.

Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6.

BACKGROUND: Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. METHODS: Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. RESULTS: In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. CONCLUSION: In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract.

Fatty acid binding protein 5 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by degradation of Krüppel-like factor 9 mediated by miR-889-5p via cAMP-response element binding protein.

Mounting evidence has demonstrated that fatty acid binding protein 5 (FABP5) is commonly upregulated in many human malignancies. However, the mechanisms explaining the involvement of FABP5 in hepatocellular carcinoma (HCC) remain unclear. In this study, we demonstrated the involvement of FABP5 and its downstream signaling molecules in HCC progression. We first confirmed that FABP5 expression was upregulated in HCC. Additionally, FABP5 promoted HCC cells proliferation, migration, and invasion. Mechanistic investigation showed that FABP5 could improve cAMP-response element binding protein (CREB) phosphorylation. Meanwhile, CREB, as a transcription factor, upregulated the miR-889-5p expression by binding to the miR-889-5p promoter region. Consequently, miR-889-5p led to downregulation of Krüppel-like factor 9 (KLF9) by binding to the 3'-UTR of the KLF9 mRNA, potentiating the PI3K/AKT signaling pathway and promoting the proliferation, migration, and invasion of HCC cells. Our findings have identified a FABP5/CREB/miR-889-5p/KLF9 axis for HCC progression, and we postulate that blocking this key signaling pathway may represent a promising strategy for HCC treatment.

Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2-Dicer Signaling Pathway.

Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of hepatocellular carcinoma; however, the underlying mechanisms involved are not fully understood. In this study, using a customized, pressure-loading device, we assess the effect of pressure loading on DNA damage in human hepatocytes. We show that pressure loading leads to DNA damage and S-phase arresting in the cell cycle, and activates the DNA damage response in hepatocytes. Meanwhile, pressure loading upregulates Dicer expression, and its silencing exacerbates pressure-induced DNA damage. Moreover, pressure loading also activates ERK1/2 signaling molecules. Blockage of ERK1/2 signaling inhibits pressure-upregulated Dicer expression and exacerbates DNA damage by suppressing DNA damage response in hepatocytes. Our findings demonstrate that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, which provides evidence for a better understanding of the link between the altered mechanical environment and liver diseases.

Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model.

Increasing evidence highlights the importance of gut microbiota and its metabolites as an environmental factor affecting ischemic stroke. However, the role of microbial indole metabolites in ischemic stroke remains largely unknown. Here, we evaluated the effects and the underlying mechanism of indole-3-propionic acid (IPA) in a mouse model of acute middle cerebral artery occlusion (MCAO) and the mechanisms underlying these effects. We collected blood samples and evaluated serum indole derivatives levels using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS) in 8-10-week-old male C57 mice undergoing MCAO or sham. Intragastric IPA administration (400 µg/20 g/d) was performed in mice with MCAO, and its effects and mechanisms were assessed. We found that the serum IPA levels were significantly lower in mice with MCAO than in sham-treated subjects. 16S rRNA gene sequencing revealed that IPA treatment ameliorated the MCAO-induced alterations of the gut microbiome structure, specifically reshaping the microbial community composition in mice with MCAO to resemble that in the mice from the control group, with an increase in the abundance of probiotics and a decrease in the abundance of harmful bacteria. IPA repaired the integrity of the intestinal barrier and regulated the activities of regulatory T cells (Tregs) and Th17 cells in the gut-associated lymphoid tissue. Intragastric IPA administration effectively alleviated neuroinflammation, neurological impairment and brain infarction. Of note, Tregs in the IPA treatment group inhibited A1 reactive astrogliosis in vitro. The beneficial effects of IPA are thus mediated by the gut microbiota, which could enable the development of prebiotics for microbiome-based treatments for ischemic stroke.

Intervention Effect of Traditional Chinese Medicine Hot Pressing Combined with Health Education on the Adolescent's Visual Fatigue.

To explore the intervention effect of traditional Chinese medicine hot pressing combined with health education in adolescents with asthenopia, 92 adolescents with asthenopia admitted to the outpatient department of Guangming Traditional Chinese Medicine Hospital in Pudong New Area from October 2019 to January 2021 were selected and randomly divided into two groups: the control group and the test group, each with 46 cases. Both received health education. The control group was given sodium hyaluronate eye drops, and the test group was given traditional Chinese medicine hot ironing technique intervention. After 2 courses of treatment, the scores of visual fatigue symptoms, clinical curative effect, and eye refractive power of the two groups were observed. The satisfaction of treatment was compared between the two groups. The scores of asthenopia of the two groups were compared at 6 months after intervention. After the intervention, the scores of visual fatigue symptoms in the control group and the test group were reduced after one or two courses of treatment (control group: t = 4.167, 6.318, and P=0.027, 0.010; test group: t = 4.820, 6.834, and P=0.013, <0.001). The scores of asthenopia symptoms of the trial group after the intervention for one and two courses were significantly lower than those of the control group (P < 0.05); the total clinical effective rate of the trial group was 93.48%, which was significantly higher than that of the control group (80.43%). The difference between the groups was statistically significant (P < 0.05); the left and right eyes of the control group did not change significantly before and after the intervention (P > 0.05). After the intervention, the left and right eyes of the paper group were significantly reduced (P < 0.05). After the intervention, the difference of the two groups in the refractive power of the left and right eyes was statistically significant (P < 0.05). After treatment, the satisfaction of the experimental group was significantly higher than that of the control group (P < 0.05). After 6 months, there was no significant change in the visual fatigue score of the experimental group, while the visual fatigue score of the control group increased significantly. The traditional Chinese medicine ironing combined with health education intervention can improve the symptoms of adolescents' asthenopia and improve the treatment efficiency. The method is safe, and the operation is convenient. It is worthy of clinical promotion.

Machine learning-based prognostic and metastasis models of kidney cancer.

Background: Kidney cancer originates from the urinary tubule epithelial system of the renal parenchyma, accounting for 20% of all urinary system tumors. Approximately 70% of cases are localized at diagnosis, and 30% are metastatic. Most localized kidney cancers can be cured by surgery, but most metastatic patients relapse after surgery and eventually die of kidney cancer. Therefore, accurately predicting patient survival and identifying high-risk metastatic patients will effectively guide interventions and improve prognosis. Methods: This study used the data of 12,394 kidney cancer patients from the surveillance, epidemiology, and end results database to construct a research cohort related to kidney cancer survival and metastasis. Eight machine learning models (including support vector machines, logistic regression, decision tree, random forest, XGBoost, AdaBoost, K-nearest neighbors, and multilayer perceptron) were developed to predict the survival and metastasis of kidney cancer and six evaluation indicators (accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic [AUROC]) were used to verify, evaluate, and optimize the models. Results: Among the eight machine learning models, Logistic Regression has the highest AUROC in both prediction scenarios. For 3-year survival prediction, the Logistic Regression model had an accuracy of 0.684, a sensitivity of 0.702, a specificity of 0.670, a precision of 0.686, an F1 score of 0.683, and an AUROC of 0.741. For tumor metastasis prediction, the Logistic Regression model had an accuracy of 0.800, a sensitivity of 0.540, a specificity of 0.830, a precision of 0.769, an F1 score of 0.772, and an AUROC of 0.804. Conclusion: In this study, we selected appropriate variables from both statistical and clinical significance and developed and compared eight machine learning models for predicting 3-year survival and metastasis of kidney cancer. The prediction results and evaluation results demonstrated that our model could provide decision support for early intervention for kidney cancer patients.

Prognostic Value and Molecular Mechanisms of Proteasome 26S Subunit, Non-ATPase Family Genes for Pancreatic Ductal Adenocarcinoma Patients after Pancreaticoduodenectomy.

Objective: Pancreatic cancer (PC) is an extremely malignant tumor with similar morbidity and mortality and lack of an effective treatment. This study explored the prognostic value and molecular mechanisms of proteasome 26S subunit, non-ATPase (PSMD) family genes in pancreatic ductal adenocarcinoma (PDAC).Methods: Survival analyses were performed to elucidate the relationship between prognosis and the level of PSMD expression. ROC curves and nomograms were constructed to predict the prognosis. A bioinformatics analysis was used to explore the co-expression and complex interaction networks of PSMDs. The potential mechanisms were further explored via gene set enrichment analysis (GSEA).Results: We find high levels of PSMD6, PSMD9, PSMD11, and PSMD14 expression were significantly associated with a poorer OS. High PSMD6 and PSMD11 expression was associated with a poorer relapse-free survival (RFS). A risk score model was constructed based on prognosis-related genes. The area under ROC curves (AUC) was 53.3%, 59.3%, and 62.9% for 1-, 2-, 3 years, respectively.Conclusion: GSEA revealed that PSMD6 and PSMD11 play a role in PDAC through various biological processes and signaling pathways, including TP53, CDKN2A, MYC pathway, DNA repair, KRAS, cell cycle checkpoint, NIK, NF-κB signaling pathway, and proteasomes. This study demonstrated that PSMD6 and PSMD11 could serve as a potential prognostic and diagnostic biomarkers for patients with early-stage PDAC after pancreaticoduodenectomy.

Systematic Analysis of the Clinical Significance of Hyaluronan-Mediated Motility Receptor in Colorectal Cancer.

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines. Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples. Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC. Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.