[Efficacy analysis of 23 cases of parapharyngeal space tumors removed by oral approach assisted by plasma and high-definition endoscopic system].

Objective:To explore the selection, efficacy and application of indications for parapharyngeal space tumor resection assisted by plasma and HD endoscopic system through oral approach. Methods:The clinical data of 23 patients with parapharyngeal space tumor resection assisted by plasma and HD endoscopic system were retrospectively analyzed in Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Bengbu Medical University from January 2013 to June 2023. All cases were examined by high-resolution CT and MRI before operation, and some cases were examined by CTA or DSA. During the operation, the high definition nasal endoscopic recording system was assisted, and low temperature plasma knife was used in some cases. The follow-up time was from 3 to 115 months, and the median follow-up time was 45 months. Results:There were no deaths in this group. All patients had complete tumor resection. The maximum tumor diameter was as follows: （5.20±1.00） cm, the operation time was（128.70±46.67） min, and the average blood loss was（80.87±32.74） mL. One case of vascular smooth muscle tumor had more bleeding during the operation and was assisted by tracheotomy after operation. One case of nourishing vascular bleeding after operation of giant Schwannoma was investigated and hemostasis + external carotid artery ligation. Bleeding in the remaining cases was below 120 mL. Postoperative pathologies were all benign tumors, including 11 pleomorphic adenoma, 4 schwannoma, 2 base cell adenoma, 1 epidermoid cyst, 1 lymphatic cyst with infection, 1 angiomyoma, 1 solitary fibroma, 1 salivary gland cyst, and 1 tendon giant cell tumor. All patients were followed up. One patient originating from vagal schwannoma had 2-month vocal cord paralysis and 1 recurrence（recurrence of the skull base of schwannoma）. Conclusion:Oral approach assisted by plasma and high-definition endoscopic system is suitable for partial selective resection of benign tumors in parapharyngeal space, which has the advantages of less trauma and rapid recovery. When the tumor is blood-rich, suspected to be malignant, the top of the tumor is deep into the cranial base nerve canal,located outside the internal carotid artery, and larger than 6.0 cm considering pleomorphic adenoma, it is recommended to conduct an external open or auxiliary cervical small incision approach.

Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study.

BACKGROUND: In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. METHODS: Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR. RESULTS: During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04-2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23-5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1-2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05). CONCLUSION: High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.

CircTNPO1 promotes the tumorigenesis of osteosarcoma by sequestering miR-578 to upregulate WNT5A expression.

As a type of non-coding RNAs, circular RNAs (circRNAs) have the ability to bind to miRNAs and regulate gene expression. Recent studies have shown that circRNAs are involved in certain pathological events. However, the expression and functional role of circTNPO1 in osteosarcoma (OS) are not yet clear. To investigate circRNAs that are differentially expressed in OS tissues and cells, circRNA microarray analysis combined with qRT-PCR was performed. The in-vitro and in-vivo functions of circTNPO1 were studied by knocking it down or overexpressing it. The binding and regulatory relationships between circTNPO1, miR-578, and WNT5A were evaluated using dual luciferase assays, RNA pull-down and rescue assays, as well as RNA immunoprecipitation (RIP). Furthermore, functional experiments were conducted to uncover the regulatory effect of the circTNPO1/miR-578/WNT5A pathway on OS progression. Cytoplasm was identified as the primary location of circTNPO1, which exhibited higher expression in OS tissues and cells compared to the corresponding controls. The overexpression of circTNPO1 was found to enhance malignant phenotypes in vitro and increase oncogenicity in vivo. Moreover, circTNPO1 was observed to sequester miR-578 in OS cells, resulting in the upregulation of WNT5A and promoting carcinoma progression. These findings indicate that circTNPO1 can contribute to the progression of OS through the miR-578/WNT5A axis. Therefore, targeting the circTNPO1/miR-578/WNT5A axis could be a promising therapeutic strategy for OS.

SIRT3 ameliorates diabetes-associated cognitive dysfunction via regulating mitochondria-associated ER membranes.

BACKGROUND: Diabetes is associated with an increased risk of cognitive decline and dementia. These diseases are linked with mitochondrial dysfunction, most likely as a consequence of excessive formation of mitochondria-associated membranes (MAMs). Sirtuin3 (SIRT3), a key mitochondrial NAD+-dependent deacetylase, is critical responsible for mitochondrial functional homeostasis and is highly associated with neuropathology. However, the role of SIRT3 in regulating MAM coupling remains unknown. METHODS: Streptozotocin-injected diabetic mice and high glucose-treated SH-SY5Y cells were established as the animal and cellular models, respectively. SIRT3 expression was up-regulated in vivo using an adeno-associated virus in mouse hippocampus and in vitro using a recombinant lentivirus vector. Cognitive function was evaluated using behavioural tests. Hippocampus injury was assessed using Golgi and Nissl staining. Apoptosis was analysed using western blotting and TUNEL assay. Mitochondrial function was detected using flow cytometry and confocal fluorescence microscopy. The mechanisms were investigated using co-immunoprecipitation of VDAC1-GRP75-IP3R complex, fluorescence imaging of ER and mitochondrial co-localisation and transmission electron microscopy of structural analysis of MAMs. RESULTS: Our results demonstrated that SIRT3 expression was significantly reduced in high glucose-treated SH-SY5Y cells and hippocampal tissues from diabetic mice. Further, up-regulating SIRT3 alleviated hippocampus injuries and cognitive impairment in diabetic mice and mitigated mitochondrial Ca2+ overload-induced mitochondrial dysfunction and apoptosis. Mechanistically, MAM formation was enhanced under high glucose conditions, which was reversed by genetic up-regulation of SIRT3 via reduced interaction of the VDAC1-GRP75-IP3R complex in vitro and in vivo. Furthermore, we investigated the therapeutic effects of pharmacological activation of SIRT3 in diabetic mice via honokiol treatment, which exhibited similar effects to our genetic interventions. CONCLUSIONS: In summary, our findings suggest that SIRT3 ameliorates cognitive impairment in diabetic mice by limiting aberrant MAM formation. Furthermore, targeting the activation of SIRT3 by honokiol provides a promising therapeutic candidate for diabetes-associated cognitive dysfunction. Overall, our study suggests a novel role of SIRT3 in regulating MAM coupling and indicates that SIRT3-targeted therapies are promising for diabetic dementia patients.

Efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD: A systematic review and meta-analysis.

OBJECTIVE: The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD. METHODS: Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I2 statistic was used to assess heterogeneity, and meta-analysis was performed when possible. RESULTS: Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61). CONCLUSION: This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients. CLINICAL TRIAL REGISTRATION: PROSPERO; No: CRD42022369112; URL: https://www.crd.york.ac.uk/prospero/.

A systematic pharmacology-based in vivo study to reveal the effective mechanism of Yupingfeng in asthma treatment.

BACKGROUND: The clinical effect of Yupingfeng (YPF) has been confirmed in asthma patients, however, it lacks a study to verify its pharmacological mechanism. HYPOTHESIS/PURPOSE: To reveal the molecular basis and potential pharmacological mechanism of YPF in the treatment of asthma. STUDY DESIGN AND METHODS: First, a systems pharmacology-based method integrating pharmacokinetic screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of YPF in asthma. Second, differentially expressed genes (DEGs) between asthma patients and healthy controls were identified by GEO2R online tool. Third, based on systems pharmacology and DEGs results, molecular docking was performed utilizing the Discovery Studio 2020 Client version to detect the binding capacity between compounds and targets. Finally, ovalbumin (OVA)-challenged C57BL/6 mice were treated with YPF or its effective compound to assess the predictions. RESULTS: A total of 35 active compounds were filtered out, with 87 potential targets being identified for further analysis after target fishing and matching. Quercetin, kaempferol, and wogonin were identified as the main ingredients in YPF. The signaling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), tumor necrosis factor (TNF) and IL-17 were identified as the top signaling pathways in KEGG enrichment analysis. GEO2R tools of NCBI discovered five DEGs that overlapped with the therapeutic targets of YPF. Wogonin was proven to be the top active compound in YPF through the results of molecular docking. In vivo experiments indicated that YPF and wogonin significantly attenuated airway resistance and lung inflammation by decreasing the levels of inflammatory cytokines and key factors in PI3K/AKT, IL-17, and TNF signaling pathways. CONCLUSIONS: YPF and its main active compound wogonin may exert some therapeutic effects on asthma inflammation through multiple molecular targets and signaling pathways including PI3K/AKT, IL-17 and TNF-α.

Development and external validation of a prognosis model to predict outcomes after curative resection of early-stage intrahepatic cholangiocarcinoma.

Background: Early-stage intrahepatic cholangiocarcinoma (ESICC) with curative resection and lymph node-negative still has the risk of poor prognosis, and there lacks prognosis-assessing tools for these patients. The objective of this study was to develop a prognosis model to predict outcomes and identify risk stratification for ESICC after resection. Methods: Totally 263 patients with ESICC after hepatectomy from January 2012 to January 2022 were analyzed. Clinicopathological factors were selected using multivariable Cox regression analysis and a prognosis model was developed. The performance of the model was evaluated by concordance index (C-index), calibration plots, decision curves analysis (DCA), and net reclassification index (NRI). Kaplan-Meier curves were analyzed for risk stratification of overall survival (OS) and recurrence-free survival (RFS) based on the prognosis model. Results: The clinicopathological features that were independently associated with OS of ESICC included carbohydrate antigen19-9, carcinoembryonic antigen, tumor size, tumor differentiation, and T stage. The prognosis model based on these prognostic factors demonstrated excellent discriminatory performance in both derivation cohort (C-index, 0.71) and external validation cohort (C-index, 0.78), which outperformed the TNM staging system (C-index, 0.59) and individual prognostic factors (all C-index < 0.7). Calibration plots, DCA and NRI also showed superior predictive performance. According to the risk for survival, the model stratified patients into low risk (median OS, 66.6 months; median RFS, 24.3 months) and high risk (median OS, 24.0 months; median RFS, 6.4 months) (P < 0.001). Conclusions: Our prognosis model can robustly predict the outcomes of ESICC after curative resection and provide precise evaluation on prognosis risk, facilitating clinicians to develop individualized postoperative treatment options.

Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity.

The use of chemotherapeutic agents is becoming more frequent as the proportion of new oncology patients increases worldwide, with prolonged survival after treatment. As one of the most popular chemotherapy drugs, doxorubicin plays a substantial role in the treatment of tumors. Unfortunately, the use of doxorubicin is associated with several adverse effects, particularly severe cardiotoxicity that can be life-threatening, which greatly limits its clinical use. For decades, scientists have tried to explore many cardioprotective agents and therapeutic approaches, but their efficacy remains controversial, and some drugs have even brought about significant adverse effects. The concrete molecular mechanism of doxorubicin-induced cardiotoxicity is still to be unraveled, yet endothelial damage is gradually being identified as an important mechanism triggering the development and progression of doxorubicin-induced cardiotoxicity. Endothelial-to-mesenchymal transition (EndMT), a fundamental process regulating morphogenesis in multicellular organisms, is recognized to be associated with endothelial damage repair and acts as an important factor in the progression of cardiovascular diseases, tumors, and rheumatic immune diseases. Mounting evidence suggests that endothelial-mesenchymal transition may play a non-negligible role in doxorubicin-induced cardiotoxicity. In this paper, we reviewed the molecular mechanisms and signaling pathways of EndMT and outlined the molecular mechanisms of doxorubicin-induced cardiotoxicity and the current therapeutic advances. Furthermore, we summarized the basic principles of doxorubicin-induced endothelial-mesenchymal transition that lead to endothelial dysfunction and cardiotoxicity, aiming to provide suggestions or new ideas for the prevention and treatment of doxorubicin-induced endothelial and cardiac injury.

Identification of Hypoxia-related Genes in Acute Myocardial Infarction using Bioinformatics Analysis.

BACKGROUND: Acute myocardial infarction (AMI) remains one of the most fatal diseases worldwide. Persistent ischemia and hypoxia are implicated as significant mechanisms in the development of AMI. However, no hypoxia-related gene targets of AMI have been identified to date. This study aimed to identify potential genes and drugs for AMI using bioinformatics analysis. MATERIALS AND METHODS: Two datasets both related to AMI (GSE76387 and GSE161427) were downloaded from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between AMI and sham mice. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes using Cytoscape. Candidate genes were identified by the intersection of hub genes and hypoxia-related genes. Western blotting was used to validate the candidate genes in the AMI mouse model. Furthermore, the Drug-Gene Interaction Database was used to predict potential therapeutic drugs targeting all hub genes. RESULTS: Fifty-three upregulated and 16 downregulated genes closely related to AMI were identified. The DEGs were primarily enriched in protein, heparin, and integrin binding. KEGG analysis suggested that focal adhesion, PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction are crucial pathways for AMI. The PPI network analysis identified 14 hub genes, two of which were hypoxia-related. Several agents were found to have therapeutic potential for AMI. CONCLUSION: This study suggests that connective tissue growth factors and the collagen family members may be candidate targets in treating AMI. Agents targeting these candidates may be potential treatments.

Ultrashort 15-nm flexible radio frequency ITO transistors enduring mechanical and temperature stress.

Flexible radio frequency (RF) transistors play an important role in the fast-growing wearable smart sensors for data communication. However, the scaling capability and high-speed performance of the flexible transistor are far below the counterparts on rigid substrates, impeding the gigahertz high-speed applications. Here, we address the scaling and performance bottlenecks in flexible transistors by demonstrating natively flexible RF indium tin oxide transistors with deeply scaled 15-nm-long channel, capable of operating in the 10-GHz frequency range. The record-high cutoff frequency of 11.8 GHz and maximum oscillation frequency of 15 GHz can rival those on rigid substrates. Furthermore, the robustness of flexible RF transistors was examined, capable of enduring heavy-duty 10,000 bending cycles at 1-mm radius and extreme thermal stress from cryogenic temperature of 4.3 K and high temperature of 380 K.

Protein Kinase RhCIPK6 Promotes Petal Senescence in Response to Ethylene in Rose (Rosa Hybrida).

Cultivated roses have the largest global market share among ornamental crops. Postharvest release of ethylene is the main cause of accelerated senescence and decline in rose flower quality. To understand the molecular mechanism of ethylene-induced rose petal senescence, we analyzed the transcriptome of rose petals during natural senescence as well as with ethylene treatment. A large number of differentially expressed genes (DEGs) were observed between developmental senescence and the ethylene-induced process. We identified 1207 upregulated genes in the ethylene-induced senescence process, including 82 transcription factors and 48 protein kinases. Gene Ontology enrichment analysis showed that ethylene-induced senescence was closely related to stress, dehydration, and redox reactions. We identified a calcineurin B-like protein (CBL) interacting protein kinase (CIPK) family gene in Rosa hybrida, RhCIPK6, that was regulated by age and ethylene induction. Reducing RhCIPK6 expression through virus-induced gene silencing significantly delayed petal senescence, indicating that RhCIPK6 mediates petal senescence. In the RhCIPK6-silenced petals, several senescence associated genes (SAGs) and transcription factor genes were downregulated compared with controls. We also determined that RhCIPK6 directly binds calcineurin B-like protein 3 (RhCBL3). Our work thus offers new insights into the function of CIPKs in petal senescence and provides a genetic resource for extending rose vase life.

Valve implantation for successful sealing of a balloon predilatation-induced annular rupture during transcatheter aortic valve replacement.

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.

Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy.

Various types of progenitors initiate individual organ formation and their crosstalk orchestrates morphogenesis for the entire embryo. Here we show that progenitor exosomal communication across embryonic organs occurs in normal development and is altered in embryos of diabetic pregnancy. Endoderm fibroblast growth factor 2 (FGF2) stimulates mesoderm Flk-1+ vascular progenitors to produce exosomes containing the anti-stress protein Survivin. These exosomes act on neural stem cells of the neuroepithelium to facilitate neurulation by inhibiting cellular stress and apoptosis. Maternal diabetes causes Flk-1+ progenitor dysfunction by suppressing FGF2 through DNA hypermethylation. Restoring endoderm FGF2 prevents diabetes-induced survivin reduction in Flk-1+ progenitor exosomes. Transgenic Survivin expression in Flk-1+ progenitors or in utero delivery of survivin-enriched exosomes restores cellular homeostasis and prevents diabetes-induced neural tube defects (NTDs), whereas inhibiting exosome production induces NTDs. Thus, functional inter-organ communication via Flk-1 exosomes is vital for neurulation and its disruption leads to embryonic anomalies.

Overexpressed RING Finger 44 Correlates with Poor Prognosis in Hepatocellular Carcinoma.

Introduction: Liver carcinoma is one of the most common cancers in the world and remains one of the most difficult cancers to treat. Hepatocellular cancer is the most important type of liver cancer (90%). RING Finger 44 (RNF44) is one of the E3 ligases, which play an important role in substrate recognition. It was also reported that RING Finger 44 was connected with resistant melanoma. But the relationship between RNF44 and HCC remained unknown. Materials and Methods: To analyze the role of RING Finger 44 gene in hepatocellular carcinoma, we used bioinformatics to analyze the expression level, genetic changes, immunohistochemistry, immune infiltration, diagnostic value, survival, and functional enrichment of RING Finger 44. Results: Through analyzing The Genotype-Tissue Expression and The Cancer Genome Atlas databases, we found that the expression level of RING Finger 44 was significantly increased in hepatocellular carcinoma tissues. Meanwhile, the expression of RING Finger 44 was connected with immune cell infiltration and survival time, and the expression level of RING Finger 44 could perform as a useful diagnostic and prognostic index. The functional enrichment analysis of RING Finger 44 provided some possible pathways of RING Finger 44 in hepatocellular carcinoma, which provided an important direction for the further experiments in vitro or in vivo. Conclusions: RING Finger 44, the high expression level of which predicts poor prognosis, is a potential oncogene in hepatocellular carcinoma.

UHRF1 is indispensable for meiotic sex chromosome inactivation and interacts with the DNA damage response pathway in mice†.

During male meiosis, the constitutively unsynapsed XY chromosomes undergo meiotic sex chromosome inactivation (MSCI), and the DNA damage response (DDR) pathway is critical for MSCI establishment. Our previous study showed that UHRF1 (ubiquitin-like, with PHD and ring finger domains 1) deletion led to meiotic arrest and male infertility; however, the underlying mechanisms of UHRF1 in the regulation of meiosis remain unclear. Here, we report that UHRF1 is required for MSCI and cooperates with the DDR pathway in male meiosis. UHRF1-deficient spermatocytes display aberrant pairing and synapsis of homologous chromosomes during the pachytene stage. In addition, UHRF1 deficiency leads to aberrant recruitment of ATR and FANCD2 on the sex chromosomes and disrupts the diffusion of ATR to the XY chromatin. Furthermore, we show that UHRF1 acts as a cofactor of BRCA1 to facilitate the recruitment of DDR factors onto sex chromosomes for MSCI establishment. Accordingly, deletion of UHRF1 leads to the failure of meiotic silencing on sex chromosomes, resulting in meiotic arrest. In addition to our previous findings, the present study reveals that UHRF1 participates in MSCI, ensuring the progression of male meiosis. This suggests a multifunctional role of UHRF1 in the male germline.

Role of apolipoprotein O in autophagy via the p38 mitogen-activated protein kinase signaling pathway in myocardial infarction

Abstract Objectives To explore the role and possible mechanisms of action of apolipoprotein O (APOO) in autophagy in Myocardial Infarction (MI) in vivo and in vitro. Methods Differential gene expression and single Gene Set Enrichment Analysis (GSEA) were used to evaluate MI-related candidate genes. Animal and cell MI models were established. Sh-APOO, si-APOO, and SB203580 were used to inhibit the expression of APOO or p38MAPK. Western blot and qRT-PCR were used to analyze the expression levels of the target protein or mRNA. Apoptosis was observed using the TUNEL assay. The plasma concentrations of CK-MB and cTn-I in humans and mice were determined. Results In the GSE23294 dataset, APOO mRNA was highly expressed in the left ventricle of mice with MI; GSEA revealed that APOO was positively correlated with p38MAPK, autophagy, and apoptosis. The plasma concentration of APOO in patients with MI was significantly higher than that in healthy subjects. The expression of APOO, Beclin-1, LC3, and Bax in mouse and AC16 cell MI models increased, while the level of Bcl-2 decreased. After silencing the APOO gene, the expression of APOO was downregulated; meanwhile, changes in autophagy, apoptosis and myocardial cell injury were reversed in vivo and in vitro. Furthermore, autophagy was alleviated after AC16 cells were treated with SB203580. Conclusions The increased APOO expression in mouse and cell MI models may activate autophagy and apoptosis by regulating the p38MAPK signaling pathway, thus aggravating the myocardial injury. HIGHLIGHTS APOO was highly expressed in the left ventricle of mice with myocardial infarction. Increasing of APOO may activate autophagy and apoptosis in myocardial infarction. The regulation of APOO in autophagy and apoptosis was regulated by p38MAPK signaling pathway.

R2R3-MYB Transcription Factor PlMYB108 Confers Drought Tolerance in Herbaceous Peony (Paeonia lactiflora Pall.).

The MYB transcription factor (TF) is crucial for plant growth, development, and response to abiotic stress, but it is rarely reported in the herbaceous peony (Paeonia lactiflora Pall.). Here, an MYB TF gene was isolated, and based on our prior mRNA data from P. lactiflora samples, it was treated with drought stress (DS). Its complete cDNA structure was 1314 bp, which encoded 291 amino acids (aa). Furthermore, using sequence alignment analysis, we demonstrated that PlMYB108 was an R2R3-MYB TF. We also revealed that PlMYB108 was primarily localized in the nucleus. Its levels rose during DS, and it was positively correlated with drought tolerance (DT) in P. lactiflora. In addition, when PlMYB108 was overexpressed in tobacco plants, the flavonoid content, antioxidant enzyme activities, and photosynthesis were markedly elevated. Hence, the transgenic plants had stronger DT with a higher leaf water content and lower H2O2 accumulation compared to the wild-type (WT) plants. Based on these results, PlMYB108 is a vital gene that serves to increase flavonoid accumulation, reactive oxygen species (ROS), scavenging capacity, and photosynthesis to confer DT. The results would provide a genetic resource for molecular breeding to enhance plant DT.

Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study.

BACKGROUND: Not all patients with unresectable hepatocellular carcinoma (uHCC) benefit from treatment with immune checkpoint inhibitors and molecular-targeted agents. The aim of this retrospective study was to assess the efficacy and safety of pembrolizumab plus lenvatinib plus hepatic arterial infusion chemotherapy (HAIC) versus pembrolizumab plus lenvatinib in selected populations of patients with treatment-naive uHCC exhibiting programmed cell death ligand-1 (PD-L1) staining. METHODS: Consecutive patients with treatment-naive uHCC exhibiting PD-L1 staining who were treated with pembrolizumab plus lenvatinib plus HAIC (PLH) or pembrolizumab plus lenvatinib (PL) were retrospectively identified from our medical centres from 2018 to 2021. HAIC involved oxaliplatin, fluorouracil, and leucovorin (FOLFOX). Follow-up occurred every 3 weeks for 1 year and then every 6 weeks thereafter. The primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the frequency of key adverse events (AEs). RESULTS: In total, 248 treatment-naive patients were retrospectively reviewed, 78 of whom were ineligible on the basis of the current criteria. Thus, 170 patients (PLH: n = 84, median age 52 years [range, 42-67]; PL: n = 86, 53 years [range, 43-69]) were eligible for the analysis. The median follow-up was 18.6 months (range, 1-26). At the final follow-up, the median OS was 17.7 months (95% confidence interval [CI], 15.2-18.3) in the PLH group versus 12.6 months (95% CI, 11.1-13.7) in the PL group (hazard ratio [HR] 0.52; 95% CI, 0.36-0.75; p = 0.001). A significant difference was also detected in the median PFS (10.9 months [95% CI, 8.7-11.4] for PLH vs. 6.8 months (95% CI, 5.2-7.4) for PL; HR 0.61, 95% CI, 0.43-0.85; p = 0.001). Significant differences in the rate of the key AEs were noted between groups (79.8% for PLH vs. 62.8% for PL, p = 0.015), but these AEs were controllable. CONCLUSIONS: Among selected populations of patients with treatment-naive uHCC exhibiting PD-L1 staining, the PLH regimen may substantially improve the survival benefits compared with the PL regimen with a controllable safety profile.

Advances in the Relationship Between Pyroptosis and Diabetic Neuropathy.

Pyroptosis is a novel programmed cell death process that promotes the release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) by activating inflammasomes and gasdermin D (GSDMD), leading to cell swelling and rupture. Pyroptosis is involved in the regulation of the occurrence and development of cardiovascular and cerebrovascular diseases, tumors, and nerve injury. Diabetes is a metabolic disorder characterized by long-term hyperglycemia, insulin resistance, and chronic inflammation. The people have paid more and more attention to the relationship between pyroptosis, diabetes, and its complications, especially its important regulatory significance in diabetic neurological diseases, such as diabetic encephalopathy (DE) and diabetic peripheral neuropathy (DPN). This article will give an in-depth overview of the relationship between pyroptosis, diabetes, and its related neuropathy, and discuss the regulatory pathway and significance of pyroptosis in diabetes-associated neuropathy.

High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study.

BACKGROUND: Intravenous iron sucrose is becoming a prevailing treatment for individuals undergoing maintenance haemodialysis, but comparisons of dosing regimens are lacking. The aim of this retrospective review was to evaluate the safety and efficacy of proactively administered high-dose iron sucrose versus reactively administered low-dose iron sucrose in patients undergoing maintenance haemodialysis. METHODS: We analysed the data of 1500 individuals with maintenance haemodialysis who were treated with either high-dose iron sucrose that was proactively administered (Group HD) or low-dose iron sucrose that was reactively administered (Group LD) at the First Affiliated Hospital of Chongqing Medical University from Jan 1, 2008, to Dec 31, 2020. The primary endpoints were the cumulative doses of iron and erythropoiesis-stimulating agent; the secondary endpoints were the events of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, infection rate, and death from any cause. RESULTS: Of the 2124 individuals, 624 individuals were excluded because they met one or more of the exclusion criteria, thus resulting in 1500 individuals who were eligible for inclusion in the study (Group HD, n = 760 and Group LD, n = 740). The median follow-up for the two cohorts was 32 months (range: 25-36). A significant median difference was detected in the monthly iron dose between the groups (1121 mg [range: 800-1274] in the HD group vs. 366 mg [range: 310-690] in the LD group; p < 0.05). The median dose of an erythropoiesis-stimulating agent was 26,323 IU/month (range: 17,596-44,712) in the HD group and 37,934 IU/month (range: 22,402-59,380) in the LD group (median difference: - 7901 IU/month; 95% CI: - 9632--5013; p = 0.000). A significant difference was detected in the secondary endpoints (266 events in 320 cases in the HD group vs. 344 events in 385 cases in the LD group) (HR: 0.62; 95% CI: 0.51-0.79; p < 0.001). A significant difference was not observed in death from any cause (HR: 0.57; 95% CI: 0.48-1.00; p = 0.361). CONCLUSIONS: For individuals undergoing maintenance haemodialysis, high-dose iron sucrose that was proactively administered may be superior to low-dose iron sucrose that was reactively administered with low doses of erythropoiesis-stimulating agent.