Intervention model under the Omaha system framework can effectively improve the sleep quality and negative emotion of patients with mid to late-stage lung cancer and is a protective factor for quality of life.

This study aims to evaluate the effects of Omaha System framework interventions on quality of life, emotional well-being, and sleep quality in 507 mid to late-stage lung cancer patients. Retrospectively, we compared data of 294 patients receiving conventional care (conventional group) with 213 patients undergoing Omaha System interventions (intervention group) from January 2019 to January 2023. Key indicators included quality of life (FACT-L), anxiety (SAS), depression (SDS), sleep quality (PSQI), hope (HHS), and dignity (PDI). Post-intervention, the intervention group showed a significant increase in FACT-L scores (P<0.001), indicating enhanced quality of life. There was a notable reduction in PSQI scores (P<0.001), suggesting improved sleep quality. Additionally, their anxiety and depression levels significantly decreased, as evidenced by lower SAS (P<0.001) and SDS scores (P<0.001). Logistic regression revealed that care nursing intervention scheme (P=0.007), age (P=0.008), marital status (P=0.002), per capita monthly household income (P=0.004), SAS after intervention (P=0.002), and PSQI after intervention (P=0.002) had a positive influence on quality of life. In conclusion, the Omaha System interventions markedly improved the quality of life, emotional state, and sleep in lung cancer patients.

Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control.

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

Novel copy number variations and phenotypes of infantile epileptic spasms syndrome.

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11-q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure-free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti-seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly.

[Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area].

OBJECTIVE: To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area. METHODS: The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes. RESULTS: Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05). CONCLUSION: The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

Natural killer cell therapy targeting cancer stem cells: Old wine in a new bottle.

A small proportion of cancer cells that have stem cell-like properties are known as cancer stem cells (CSCs). They can be used to identify malignant tumor phenotypes and patients with poor prognosis. Targeting these cells has been shown to improve the effectiveness of cancer therapies. Owing to the nature of CSCs, they are resistant to conventional treatment methods such as radio- and chemotherapy. Therefore, more effective anti-CSC therapies are required. Immunotherapy, including natural killer (NK) and T cell therapy, has demonstrated the ability to eliminate CSCs. NK cells have demonstrated superior anti-CSC capabilities compared to T cells in recognizing low levels of major histocompatibility complex (MHC) class I expression. However, CSC escape also occurs during NK cell therapy. It is important to determine CSC-specific immune evasion mechanisms and find out potential solutions to optimize NK cell function. Therefore, this review discusses promising strategies that can improve the efficiency of NK cell therapy in treating CSCs, and aims to provide a reference for future research.

Immunogenetic polymorphisms predict therapeutic efficacy and survival outcomes in tumor patients receiving PD-1/PD-L1 blockade.

BACKGROUND: While immune checkpoint inhibitors (ICIs) demonstrate remarkable clinical responses, only a small subset of patients obtains benefits. Genes linked to the tumor immune system are confirmed to be critical for the treatment of ICIs, and their polymorphisms can contribute to ICI efficacy. Here, we examined the potential of immunogenetic variations to predict the efficacy and survival of the PD-1/PD-L1 blockade. METHODS: Cancerous patients receiving PD-1/PD-L1 blockade were recruited and followed up. Pivotal genes related to tumor-immunity were filtered through a protein-protein interaction network and the degree algorithm in Cytoscape. Finally, 39 genetic variants were genotyped through multiplex genotyping assays. Association analyses between variants and ICI efficacy and progression-free survival (PFS) were performed. RESULTS: Overall, 318 patients were ultimately enrolled. Hence, three immunogenetic variants were identified as predictors of PD-1/PD-L1 blockade response. Mutant alleles from ATG7 rs7625881, CD274 rs2297136, and TLR4 rs1927911 were all at increased risk of tumor progression following ICI therapy (OR: 1.475, 1.641, 1.462, respectively; P value: 0.028, 0.017, 0.027, respectively). Significant immunogenetic variants also attained similar trends in the PD-1 blockade, lung cancer, or lung cancer using PD-1 blockade subgroups. Furthermore, the mutant genotypes of CD274 rs2297136 (GG as the reference: HR: 0.50 (95%CI: 0.29-0.88), P value: 0.015) and TLR4 rs1927911 (AA as the reference: HR: 0.65 (95%CI: 0.47-0.91), P value: 0.012) indicated poorer PFS and were both independent prognostic factors. CONCLUSION: Immunogenetic polymorphisms, including ATG7 rs7625881, CD274 rs2297136, and TLR4 rs1927911, were first identified as potential predictors of response to PD-1/PD-L1 blockade in tumor patients.

IL-10 Promotes CXCL13 Expression in Macrophages Following Foot-and-Mouth Disease Virus Infection.

Foot-and-mouth disease (FMD) is one of the most contagious livestock diseases in the world, posing a constant global threat to the animal trade and national economies. The chemokine C-X-C motif chemokine ligand 13 (CXCL13), a biomarker for predicting disease progression in some diseases, was recently found to be increased in sera from mice infected with FMD virus (FMDV) and to be associated with the progression and severity of the disease. However, it has not yet been determined which cells are involved in producing CXCL13 and the signaling pathways controlling CXCL13 expression in these cells. In this study, the expression of CXCL13 was found in macrophages and T cells from mice infected with FMDV, and CXCL13 was produced in bone-marrow-derived macrophages (BMDMs) by activating the nuclear factor-kappaB (NF-κB) and JAK/STAT pathways following FMDV infection. Interestingly, CXCL13 concentration was decreased in sera from interleukin-10 knock out (IL-10-/-) mice or mice blocked IL-10/IL-10R signaling in vivo after FMDV infection. Furthermore, CXCL13 was also decreased in IL-10-/- BMDMs and BMDMs treated with anti-IL-10R antibody following FMDV infection in vitro. Lastly, it was demonstrated that IL-10 regulated CXCL13 expression via JAK/STAT rather than the NF-κB pathway. In conclusion, the study demonstrated for the first time that macrophages and T cells were the cellular sources of CXCL13 in mice infected with FMDV; CXCL13 was produced in BMDMs via NF-κB and JAK/STAT pathways; and IL-10 promoted CXCL13 expression in BMDMs via the JAK/STAT pathway.

Effect of preoperative pulmonary artery pressure on the prognosis of end-stage heart failure patients after heart transplantation.

OBJECTIVE: To evaluate the effect of preoperative pulmonary artery pressure on perioperative outcome of end-stage heart failure patients undergoing heart transplantation. METHODS: Retrospective analysis was undertaken on the clinical data of patients receiving heart transplantation in the Department of Cardiovascular Surgery of our hospital from March 2017 to March 2022. A ROC curve analysis was developed between mean pulmonary artery pressure (mPAP) and postoperative mortality using mPAP as diagnostic criteria. Patients were divided into groups based on this threshold to determine the best mPAP threshold value for predicting postoperative nosocomial mortality, and the differences in preoperative and intraoperative data, postoperative complications, and clinical prognosis of patients in the two groups were compared. Patients were followed up to draw the survival curve of patients in the two groups. RESULTS: The study enlisted the participation of 105 patients. ROC curve research revealed that preoperative pulmonary artery pressure was substantially linked with death following heart transplantation, with mPAP = 30.5mmHg being the best threshold. The group with mPAP ≥ 30.5mmHg had a greater incidence of postoperative ECMO support (28.2% vs. 10.6%, P = 0.021) and a higher incidence of in-hospital mortality (15.4% vs. 1.5%, P = 0.019) than the group with mPAP < 30.5mmHg. The postoperative survival rates of 105 patients were 91.3%, 88.7%, 81.6%, and 77.5% at 1, 2, 3, and 4 years, respectively, however, there was no significant difference between the two groups of patients in the postoperative intermediate-far survival rate (P = 0.431). CONCLUSIONS: Preoperative pulmonary artery pressure in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off mPAP value in predicting perioperative prognosis of heart transplant recipients is 30.5mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Immunogenetic variations predict immune-related adverse events for PD-1/PD-L1 inhibitors.

BACKGROUND: PD-1/PD-L1 inhibitors have brought remarkable benefits but can cause profound immune-related adverse events (irAEs). The host immunogenetic background is likely to play a role in irAE susceptibility. In this study, we aimed to identify potential immunogenetic biomarkers to predict irAEs. METHODS: Patients with solid tumours receiving PD-1/PD-L1 blockade were recruited and followed up. Genes considered pivotal contributors to tumour-immunity and autoimmune diseases were screened out via protein-protein interaction network and Cytoscape. Consequently, thirty-nine variants in eighteen genes were genotyped using the multiplex genotyping assay. Association analysis between genetic variants and irAEs as well as irAEs-free survival was performed. RESULTS: Four immunogenetic variants as predictive biomarkers of irAEs were identified. The C allele of Mitogen-Activated Protein Kinase 1 (MAPK1) rs3810610 (odds ratio [OR] = 1.495, 95% confidence interval [CI] = 1.093-2.044, P = 0.012) was a risk predictor while the A allele of PTPRC rs6428474 (OR = 0.717, 95% CI = 0.521-0.987, P = 0.041) was a protective factor for all-grade irAEs. The A allele of ADAD1 rs17388568 (OR = 2.599, 95% CI = 1.355-4.983, P = 0.003) increased the risk while the G allele of IL6 rs1800796 (OR = 0.425, 95% CI = 0.205-0.881, P = 0.018) protected patients from high-grade irAEs. Significant immunogenetic variants reached a similar tendency in PD-1 blockade or lung cancer subgroups. In multivariate Cox regression analysis, the MAPK1 rs3810610 was an independent factor regarding all-grade irAEs-free survival (CC versus CT or TT: hazard ratio [HR] = 0.71, 95% CI = 0.52-0.99, P = 0.042). ADAD1 rs17388568 (AA versus AG or GG: HR = 0.11, 95% CI = 0.025-0.49, P = 0.004) and IL6 rs1800796 (GG or GC versus CC: HR = 3.10, 95% CI = 1.315-7.29, P = 0.01) were independent variables for high-grade irAEs-free survival. CONCLUSION: We first identified several immunogenetic polymorphisms associated with irAEs and irAEs-free survival in PD-1/PD-L1 blockade-treated tumour patients, and they may serve as potential predictive biomarkers.

Predicting effectiveness of anti-VEGF injection through self-supervised learning in OCT images.

Anti-vascular endothelial growth factor (Anti-VEGF) therapy has become a standard way for choroidal neovascularization (CNV) and cystoid macular edema (CME) treatment. However, anti-VEGF injection is a long-term therapy with expensive cost and may be not effective for some patients. Therefore, predicting the effectiveness of anti-VEGF injection before the therapy is necessary. In this study, a new optical coherence tomography (OCT) images based self-supervised learning (OCT-SSL) model for predicting the effectiveness of anti-VEGF injection is developed. In OCT-SSL, we pre-train a deep encoder-decoder network through self-supervised learning to learn the general features using a public OCT image dataset. Then, model fine-tuning is performed on our own OCT dataset to learn the discriminative features to predict the effectiveness of anti-VEGF. Finally, classifier trained by the features from fine-tuned encoder as a feature extractor is built to predict the response. Experimental results on our private OCT dataset demonstrated that the proposed OCT-SSL can achieve an average accuracy, area under the curve (AUC), sensitivity and specificity of 0.93, 0.98, 0.94 and 0.91, respectively. Meanwhile, it is found that not only the lesion region but also the normal region in OCT image is related to the effectiveness of anti-VEGF.

Effects of Particle Diameter and Inlet Flow Rate on Gas-Solid Flow Patterns of Fluidized Bed.

The complex multiscale characteristics of particle flow are notoriously difficult to predict. In this study, the evolution process of bubbles and the variation of bed height were investigated by conducting high-speed photographic experiments to verify the reliability of numerical simulations. The gas-solid flow characteristics of bubbling fluidized beds with different particle diameters and inlet flow rates were systematically investigated by coupling computational fluid dynamics (CFD) and discrete element method (DEM). The results show that the fluidization in the fluidized bed will change from bubbling fluidization to turbulent fluidization and finally to slugging fluidization, and the conversion process is related to the particle diameter and inlet flow rate. The characteristic peak is positively correlated with the inlet flow rate, but the frequency corresponding to the characteristic peak is constant. The time required for the Lacey mixing index (LMI) to reach 0.75 decreases with increasing inlet flow rate; at the same diameter, the inlet flow rate is positively correlated with the peak of the average transient velocity; and as the diameter increases, the distribution of the average transient velocity curve changes from "M" to linear. The results of the study can provide theoretical guidance for particle flow characteristics in biomass fluidized beds.

BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists.

BACKGROUND: The prognosis of B-cell acute lymphoblastic leukemia (B-ALL) has improved significantly with current first-line therapy, although the recurrence of B-ALL is still a problem. Toll-like receptor 9 (TLR9) agonists have shown good safety and efficiency as immune adjuvants. Apart from their immune regulatory effect, the direct effect of TLR9 agonists on cancer cells with TLR9 expression cannot be ignored. However, the direct effect of TLR9 agonists on B-ALL remains unknown. METHODS: We discussed the relationship between TLR9 expression and the clinical characteristics of B-ALL and explored whether CpG 685 exerts direct apoptotic effect on B-ALL without inhibiting normal B-cell function. By using western blot, co-immunoprecipitation, immunofluorescence co-localization, and chromatin immunoprecipitation, we explored the mechanism of the apoptosis-inducing effect of CpG 685 in treating B-ALL cells. By exploring the mechanism of CpG 685 on B-ALL, the predictive biomarkers of the efficacy of CpG 685 in treating B-ALL were explored. These efficiencies were also confirmed in mouse model as well as clinical samples. RESULTS: High expression of TLR9 in B-ALL patients showed good prognosis. C-MYC-induced BAX activation was the key to the effect of CpG oligodeoxynucleotides against B-ALL. C-MYC overexpression promoted P53 stabilization, enhanced Bcl-2 associated X-protein (BAX) activation, and mediated transcription of the BAX gene. Moreover, combination therapy using CpG 685 and imatinib, a BCR-ABL kinase inhibitor, could reverse resistance to CpG 685 or imatinib alone by promoting BAX activation and overcoming BCR-ABL1-independent PI3K/AKT activation. CONCLUSION: TLR9 is not only a prognostic biomarker but also a potential target for B-ALL therapy. CpG 685 monotherapy might be applicable to Ph- B-ALL patients with C-MYC overexpression and without BAX deletion. CpG 685 may also serve as an effective combinational therapy against Ph+ B-ALL.

Allele frequency and proportion defined by circulating tumor DNA profiling predict tyrosine kinase inhibitors' therapeutic outcomes for non-small cell lung cancer.

PURPOSE: Circulating tumor DNA is more and more accessible for patients who cannot undergo biopsy. No consistent conclusion has been reached on whether frequency and proportion of mutations defined by ctDNA profiling can predict therapeutic outcomes. METHODS: One hundred patients with non-small cell lung cancer harboring activating EGFR mutations (exon 19 deletion, L858R and T790M mutation) were collected in West China hospital from December 18, 2017 to December 31, 2019. We retrospectively analyzed the frequency and proportion distribution of ctDNA mutations and its relationship with tyrosine kinase inhibitors therapeutic outcomes. RESULTS: Patients with lower frequency of sensitizing EGFR mutations (< 3%) had a longer progression-free survival (PFS) time than those with higher frequency (15 months vs. 10 months, p = 0.028). Moreover, patients with the lower ratio of T790M mutation frequency and the maximum-somatic-allele-frequency (T790M/MSAF < 30%) had a less prolonged PFS than those with higher T790M/MSAF (7 months vs. 15 months, p = 0.013). CONCLUSION: The frequency and proportion of ctDNA mutations are worth clinical attention in the prediction of therapeutic outcomes.

Repetitive Transcranial Magnetic Stimulation Reduces Neuronal Loss and Neuroinflammation in Parkinson?s Disease Through the miR-195a-5p/CREB Axis.

AIM: To elucidate the molecular mechanism underlying the repetitive transcranial magnetic stimulation (rTMS) -induced improvement in Parkinson's disease (PD). MATERIAL AND METHODS: We established a PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to SAMP8 mice. The mice were then subjected to rTMS. Motor coordination and cognition were assessed using rotarod and Morris water maze tests, respectively. Nissl staining was performed to evaluate neuronal apoptosis. Furthermore, western blotting was employed to assess the expression of tyrosine hydroxylase and brain-derived neurotrophic factor. Additionally, the levels of tumor necrosis factor-α, interferon-γ, and interleukin-6 in the cerebrospinal fluid were evaluated using specific enzyme-linked immunosorbent assay kits. The expression of miR-195a-5p and cyclic AMP-response element-binding protein (CREB) was examined using quantitative real-time polymerase chain reaction and western blotting. Dual-luciferase reporter assay was performed using primary cortical rat neurons to validate the interaction between miR-195a-5p and CREB. RESULTS: rTMS improved cognition and motor coordination as well as reduced neuronal apoptosis/ and the levels of inflammatory factors in PD mice. It downregulated the expression of miR-195a-5p but upregulated that of CREB. In primary rat cortical neurons, miR-195a-5p directly targeted CREB, and we found that miR-195a-5p suppression enhanced cognitive and motor functions in PD mice. Moreover, miR-195a-5p downregulation decreased inflammatory response and neuronal loss in the PD mice. CONCLUSION: rTMS exerted its neuroprotective effects on PD mice by regulating the miR-195a-5p/CREB axis. This finding reveals a novel mechanism through which rTMS improves PD and indicates that miR-195a-5p is a potential therapeutic target for PD treatment.

Co-hydrothermal carbonization of oil shale and rice husk: Combustion, pyrolysis characteristics, and synergistic effect.

Countries all over the world are looking for fuel to replace fossil energy due to environmental concerns and a scarcity of fossil fuels. Oil shale (OS) and rice husk (RH) are both viable fuels, although they both have issues like high ash content and poor calorific value. OS and RH were used as feedstock for high-quality fuel in this study, which uses a hydrothermal technique to provide a novel way to utilize OS and rice. At different hydrothermal temperatures (150, 200 and 250 °C), including combustion and pyrolysis processes, the thermogravimetric analyzer (TGA) was used to analyse thermal transformation characteristics of co-hydrothermal carbonization (co-HTC) of OS and RH, as well as the synergistic effects. Results showed that the co-HTC pretreatment had a significant effect on the thermal transformation behaviour of OS and RH. On the one hand, the co-HTC has higher volatile content than its calculated value. On the other hand, a synergistic effect was found in combustion processes, and this effect was the most obvious when the hydrothermal temperature was around 200 °C, and the characteristic peak of functional groups vibration was strong. Therefore, the co-HTC was considered suitable for combustion. The combination of co-HTC modification with subsequent thermochemical processes has positive implications for the energy production and utilization of organic waste.

The prognosis of preoperative preemptive intubation for acute type A aortic dissection patients: a retrospective propensity score matching study.

Background: Acute type A aortic dissection (AADA) is a life-threatening cardiovascular disease, and improving perioperative mortality remains a significant challenge. The purpose of this study is to investigate the impact of preemptive intubation under adequate sedation and analgesia on the prognosis of AADA patients under the high rupture risk. Methods: The medical records of patients diagnosed with AADA and admitted to Changhai Hospital from January 2019 to January 2020 were retrospectively reviewed. Patients were divided into two groups based on whether they received preoperative preemptive intubation in the cardiac intensive care unit (ICU) before surgery. We used propensity score matching (PSM) analysis to conduct statistical analyses on the preoperative, intraoperative, and postoperative clinical data of the two groups. Results: A total of 134 patients were eventually included in the study. One patient (3.8%) in the pre-intubation group and 15 (13.9%) in the control group died of dissection rupture before surgery. After excluding patients with dissection rupture, there were 25 patients in the pre-intubation group and 93 patients in the non-intubation group. After PSM, there were 17 patients in the pre-intubation group and 68 patients in the non-intubation group. Baseline data analysis showed that the pre-intubation group had a higher Sequential Organ Failure Assessment (SOFA) score (10.2±3.9 vs. 8.0±4.7, P=0.036) and a higher proportion of patients with coronary artery disease (16.0% vs. 1.1%, P=0.007). The rate of massive pericardial effusion was also higher in the intubation group (28.0% vs. 10.8%, P=0.049), and preoperative oxygenation index was lower (273.2±97.3 vs. 322.1±100.9, P=0.032) compared to the control group. The results showed no significant differences in intraoperative and postoperative data for the two groups. Kaplan-Meier survival curves indicated a trend towards a more favorable prognosis for patients in the preemptive intubation group, but this difference was not significant either before or after PSM. Conclusions: Preemptive pre-intubation may benefit high-risk patients with factors such as hypoxia, massive pericardial effusion, and agitation, improving the more critically AADA patients' perioperative outcomes.

Pulmonary and tricuspid regurgitation after Tetralogy of Fallot repair: A case report.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common congenital heart defects, and surgery is the primary treatment. There are no precise guidelines on the treatment protocol for tricuspid regurgitation (TR) as a common complication of TOF repair. The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine. Here, we report the first case of sequential treatment of pulmonary and TR using interventional therapy. CASE SUMMARY: We present the case of a 52-year-old female patient, who had a history of TOF repair at a young age. A few years later, the patient presented with pulmonary and tricuspid regurgitation. The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation. Preoperative testing revealed that the patient's disease had advanced to an intermediate to advanced stage and that her general health was precarious. Because open-heart surgery was not an option for the patient, transcatheter tricuspid valve replacement was suggested. This procedure was successful, and the patient recovered fully without any adverse effects. This case report may serve as a useful resource for planning future treatments. CONCLUSION: Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair. The interventional strategy could be an alternative for patients with poor general health.

Peste des Petits Ruminants Virus Upregulates STING to Activate ATF6-Mediated Autophagy.

Peste des petits ruminants virus (PPRV) infection leads to autophagy, and the molecular mechanisms behind this phenomenon are unclear. Here, we demonstrate that PPRV infection results in morphological changes of the endoplasmic reticulum (ER) and activation of activating transcription factor 6 (ATF6) of the ER stress unfolded protein response (UPR). Knockdown of ATF6 blocked the autophagy process, suggesting ATF6 is necessary for PPRV-mediated autophagy induction. Further study showed that PPRV infection upregulates expression of the ER-anchored adaptor protein stimulator of interferon genes (STING), which is well-known for its pivotal roles in restricting DNA viruses. Knockdown of STING suppressed ATF6 activation and autophagy induction, implying that STING functions upstream of ATF6 to induce autophagy. Moreover, the STING-mediated autophagy response originated from the cellular pattern recognition receptor melanoma differentiation-associated gene 5 (MDA5). The absence of MDA5 abolished the upregulation of STING and the activation of autophagy. The deficiency of autophagy-related genes (ATG) repressed the autophagy process and PPRV replication, while it had no effect on MDA5 or STING expression. Overall, our work revealed that MDA5 works upstream of STING to activate ATF6 to induce autophagy. IMPORTANCEPPRV infection induces cellular autophagy; however, the intracellular responses and signaling mechanisms that occur upon PPRV infection are obscure, and whether innate immune responses are linked with autophagy to regulate viral replication is largely unknown. Here, we uncovered that the innate immune sensor MDA5 initiated the signaling cascade by upregulating STING, which is best known for its role in anti-DNA virus infection by inducing interferon expression. We first provide evidence that STING regulates PPRV replication by activating the ATF6 pathway of unfolded protein responses (UPRs) to induce autophagy. Our results revealed that in addition to mediating responses to foreign DNA, STING can cross talk with MDA5 to regulate the cellular stress response and autophagy induced by RNA viruses; thus, STING works as an adaptor protein for cellular stress responses and innate immune responses. Modulation of STING represents a promising approach to control both DNA and RNA viruses.

Gastric mucosal precancerous lesions in Helicobacter pylori-infected pediatric patients in central China: A single-center, retrospective investigation.

BACKGROUND: Helicobacter pylori (H. pylori) infects about 50% of the world population and is the major cause of chronic gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection induces gastric mucosal precancerous lesions mostly in adulthood, and it is debatable whether these pathological conditions can occur in childhood and adolescents as well. Since this is a critical issue to determine if intervention should be offered for this population group, we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H. pylori and gastric cancer. AIM: To investigate the relationship of H. pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China. METHODS: We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients with H. pylori infection and endoscopic and histological data. H. pylori infection status was determined by rapid urease test and histopathological examination. Both clinical and pathological data were collected and analyzed retrospectively. Occurrence of gastric mucosal precancerous lesions, inflammatory activity and degree of inflammatory cell infiltration between H. pylori-positive and -negative groups were compared. RESULTS: Among the 1015 eligible children and adolescents, the overall H. pylori infection rate was 84.14% (854/1015). The infection rate increased with age. The incidence of gastric mucosal precancerous lesions in H. pylori-infected children was 4.33% (37/854), which included atrophic gastritis (17 cases), intestinal metaplasia (11 cases) and dysplasia (9 cases). In H. pylori-negative patients, only 1 atrophic gastritis case [0.62%, (1/161)] was found (P < 0.05). Active inflammation in H. pylori-infected patients was significantly higher than that in non-infected patients, and the H. pylori-infected group showed more severe lymphocyte and neutrophil granulocyte infiltration (P < 0.001). In addition, endoscopy revealed that the most common findings in H. pylori-positive patients were antral nodularity, but in H. pylori-negative patients only superficial gastritis was observed. CONCLUSION: In children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of H. pylori-infected patients in central China. These cases included atrophic gastritis, intestinal metaplasia, and dysplasia. The data revealed an obvious critical issue requiring future investigation and intervention for this population group.