Background Chlorinated perfluoroalkyl ether sulfonate Cl-PFAES, trade name F-53B, a novel per- and polyfluoroalkyl substance (PFAS), has been shown to induce multi-organ toxicity in humans and cross the blood-brain barrier. However, its toxic effects and underlying mechanisms on neural stem cells (NSCs) remain unclear. Objective To investigate the impact of F-53B on NSCs proliferation and differentiation through oxidative stress and explore its potential molecular mechanisms in associations with mitochondrial function damage and the expression of autophagy-related gene (PINK1/Parkin). Methods Primary NSCs isolated from neonatal C57BL/6 mice were used as a model and exposed to F-53B at concentrations of 0, 33, or 100 μmol·L⁻¹ for 24 h. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, while proliferation was evaluated by the 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay. Immunofluorescence staining was performed to observe differentiation phenotypes. Intracellular and mitochondrial reactive oxygen species (ROS) levels were quantified using dihydroethidium (DHE) and MitoSOX probes, respectively. Mitochondrial morphology was observed using MitoTracker Green. ATP level was measured with a commercial kit. Additionally, real-time quantitative polymerase chain reaction (qPCR) was conducted to quantify the expression of PINK1 and Parkin genes. Results Exposure to 100 μmol·L⁻¹ F-53B significantly reduced cell viability to 93.6% of the control group (P<0.01), and decreased the proportion of EdU⁺ cells (P<0.01), indicating proliferation inhibition. The differentiation analysis showed a reduction in neuronal generation, axonal shortening, and an increase in astrocytes. The 100 μmol·L⁻¹ F-53B exposure elevated intracellular ROS to 122% (P<0.01) and mitochondrial ROS (MitoROS) to 135% (P<0.001) of the control levels, leading to mitochondrial fragmentation. The ATP levels after the F-53B exposure decreased to 62.4% relative to the control group (P<0.001). Furthermore, the mRNA expression levels of PINK1 and Par after the F-53B exposure were notably reduced (P<0.05). Conclusion F-53B may induce oxidative stress, thereby disrupting mitochondrial morphology and function while inhibiting the PINK1/Parkin-mediated mitophagy pathway, ultimately leading to impaired neural stem cell proliferation and abnormal differentiation. This study provides new insights into the neurotoxicity mechanisms of F-53B.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective:To summarize and analyze the clinical outcome of minimally invasive McKeown esophagectomy for esophageal squamous cell carcinoma.Methods:We retrospectively analyzed the clinical data of patients with esophageal squamous cell carcinoma who received minimally invasive McKeown esophagectomy in Peking Union Medical College Hospital from January 2017 to December 2022. Improved anesthesia methods, monitoring of recurrent laryngeal nerve, minimally invasive gastrostomy, and jejunostomy techniques were introduced in surgical procedure. We evaluated perioperative data and long-term follow-up survival in these patients.Results:A total of 226 esophageal squamous cell carcinoma patients who met the inclusion and exclusion criteria were enrolled, of which 48.2% received neoadjuvant therapy. The mean operation time was( 327 ± 68) min, with a total of 40.5(33, 50) lymph nodes and 27(19, 33) thoracic lymph nodes harvested. The postoperative hospital stay was 9(7, 12) days, and the postoperative complication rate was 36.3%. In terms of learning curve, after 50 patients intraoperative blood loss, postoperative hospital stay, and recurrent laryngeal nerve injury rate were significantly decreased. The number of total lymph nodes, thoracic lymph nodes, and the 106tbl harvested was significantly increased. The median follow-up time was 23.5(14, 47) months, with a loss of follow-up rate of 3.5%. The overall 2-year and 5-year survival rates were 82.6% and 71.8%, respectively.Conclusion:Improved minimally invasive McKeown esophagectomy for esophageal squamous cell carcinoma are safe and acceptable. Learning curve can be shortened, with increased lymph node harvested and decreased postoperative complications, which improving the short-term and long-term outcomes of patients.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objective:To explore the potential pathogenesis of exosome-mediated polymyositis/dermatomyositis (PM/DM) through multi-omics combined with bioinformatic analysis approach and to identify potential new targets for the diagnosis and treatment of PM/DM.Methods:Collect serum exosome samples from PM/DM patients and healthy individuals who underwent physical examination in Wuxi Second People′s Hospital from January 2021 to June 2023. HiSeq high-throughput sequencing technology and iTRAQ quantitative proteomics techniques were used to perform a sequencing analysis of miRNA and protein components in serum exosomes from patients with PM/DM and healthy control. R language was adapted to conduct the limma differential analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA) functional analysis, and immunological correlation analysis. Based on these analysis, we identified core genes and established a miRNA-target gene-transcription factor co-expression molecular network. Subsequently, we employed quantitative real-time PCR (qRT-PCR) to experimentally validate the core genes. Data analysis was performed using t-test statistical analysis and receiver operating characteristic (ROC) curves were plotted to evaluate the test efficacy of the core genes. Results:Initially, 42 up-regulated differential proteins and 61 DEP down-regulated differential proteins, as well as 22 up-regulated differential miRNAs and 19 down-regulated miRNAs were screened, and 7 core genes, 13 associated differential miRNAs, and 4 transcription factors were finally identified. Based on the functional analysis we concluded that the core genes CTSG, MPO, H1-5 involved in the formation of neutrophil extracellular trap network, NF-κB pathway and other inflammation-related pathways might play an important role in exosome-mediated PM/DM pathogenesis. Immune cells such as mast cells, immature dendritic cells, natural killer cells, regulatory T cells, and helper T cells 2 were expressed to a higher extent in the disease. In the t-test, MPO [(1.08 ±0.47) vs. (2.05 ±0.62), t=-3.50, P=0.004], CTSG [(1.11 ±0.51 ) vs. (2.27 ±1.10 ), t=-2.72, P=0.022], and H1-5 [(1.03 ±0.25) vs. (1.81 ±0.73), t=-2.89, P=0.019] showed statistically significant differences. In the ROC curve analysis, MPO[AUC(95% CI): 0.92(0.78, 1)], CTSG [AUC(95% CI): 0.81(0.59, 1)], and H1-5 (AUC (95% CI)= 0.84(0.64, 1)] indicated that the three core genes had good accuracy. Conclusion:We identified the key differential molecules in serum exosomes of patients with PM/DM, and constructed a regulatory network of miRNA-target gene-transcription factor, and determined that the pathogenic mechanism of PM/DM was mediated by serum exosomes was mediated through the formation of neutrophil extracellular trapping nets and the NF-κB pathway. CTSG, MPO, and H1-5 are the core genes in the these pathways, and their related miRNAs and transcription factors have been identified, which may become potential targets and biomarkers for the diagnosis and treatment of PM/DM.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Objective:To observe the relationship between different serum sodium ion levels and hospital death in patients with chronic heart failure.Methods:The clinical data of patients hospitalized with heart failure from January 2013 to December 2018 in Shengjing Hospital of China Medical University were continuously collected, and a retrospective cohort study database was established. The study collected clinical data of 10 488 patients. Use SPSS 26.0 software to establish a database and perform statistical analysis. The patients were divided into 6 groups by different blood sodium levels, the heart failure indicators and hospital deaths among the groups were compared, the lowest death rate group (141 - 145 mmol/L) was as a reference, and univariate Logistic analysis of different blood sodium levels were performed to clarify the risk of in-hospital death from heart failure with different blood sodium levels. GraphPad Prism 5 software was used to draw Kaplan-Meier curve and analyzed the cumulative survival rate during hospitalization.Results:In 10 488 patients, there were 417 cases occurred in-hospital deaths. The range of serum sodium at admission was 108.0 - 168.0 mmol/L, and the normal reference range was 135 - 145 mmol/L. The patients were divided into 6 groups according to the blood sodium level at the time of admission: group A (<130 mmol/L), group B(130 - 135 mmol/L), group C (136 - 140 mmol/L), group D (141 - 145 mmol/L), group E (146 - 150 mmol/L), group F(≥151 mmol/L), the hospital mortality of different blood sodium groups were 14.5%, 8.6%, 3.6%, 2.4%, 5.1% and 33.3% respectively. Took the lowest in-hospital mortality group D group as a reference, 6 groups with different serum sodium were included in a single factor binary Logistic regression analysis, the results showed that increased or decreased serum sodium may increase the risk of death in the hospital for patients with heart failure. Kaplan-Meier survival analysis showed that the accumulate survival rate among the 6 groups was statistically significant ( P<0.05). Conclusions:Patients with abnormal blood sodium at admission have a higher risk of death in the hospital during the hospital stay. The in-hospital mortality rate of patients with serum sodium ions ranging from 141 to 145 mmol/L is the lowest. With the increase or decrease in serum sodium, the in-hospital mortality rate increases with the increase or decrease in serum sodium. The blood sodium level and the mortality of patients with heart failure show a "U" shape. Curve relationship. Abnormal blood sodium on admission is an independent predictor of in-hospital mortality in inpatients with heart failure.