Objective To observe the effect of esketamine on postoperative recovery in children after endoscopic adenoidectomy.Methods Sixty pediatric patients who underwent adenoidectomy with endoscope from Jan 2022 to Jan 2023 in Eye&ENT Hospital,Fudan University were enrolled.The pediatric patients were randomly divided into hydro-morphine group(n=30)and esketamine group(n=30).Anesthesia induction:lidocaine 1.5 mg/kg,propofol 2.5 mg/kg and remifentanil 4 μg/kg were injected intravenously,and then the endotracheal tube was used for airway management.Anesthesia maintenance:remifentanil infusion was at 0.2-0.5 μg·kg-1·min-1 and the end tidal concentration of sevoflurane was at 0.7-1.0 minimum alveolar concentration(MAC).At the end of surgery,either hydromorphone 0.01 mg/kg or esketamine 0.5 mg/kg were administered for postoperative pain control.Time to resume spontaneous breathing was recorded.Other parameters included respiratory rate per minute,duration of stay in the post-anesthesia care unit,hemodynamic profiles.The adverse events including agitation and desaturation were also of note.Results Children in esketamine group resumed spontaneous breathing faster(P=0.048),had faster respiratory rate when recovery of spontaneous breathing(P=0.001)and lower concentration of end tidal CO2(P=0.005).The findings suggested that esketamine did not impair respiratory function.Compared to hydro-morphine group,children in esketamine group had shorter stay in the post-anesthesia care unit with statistical difference(P=0.020).Esketamine had no effect on heart rate and blood pressure,so there were less adverse events.Conclusion Compared with 0.01 mg/kg hydro-morphine,0.5 mg/kg esketamine does not impair respiratory function and it facilitate fast recovery in children undergoing endoscopic adenoidectomy after general anesthesia.

BACKGROUND:The second heart field is crucial for the development of the embryonic heart.Abnormal development of the second heart field can result in multiple cardiac malformations.After Cx43 gene knockout,reduced formation and proliferation of cells of the second heart field can be observed,but the specific reason remains unclear. OBJECTIVE:(1)To determine whether β-catenin,Smo and Cx43 were co-expressed in the second heart field and the endoderm,we observed the expression patterns of these proteins.(2)To explore whether Cx43 interacts with the Wnt/β-catenin pathway or the Shh pathway in the development of the second heart field. METHODS:Serial paraffin sections of the mouse embryos at embryonic days 10-12 were selected for immunohistochemical staining,hematoxylin-eosin staining and immunofluorescence staining.The primitive gut of mouse embryos at embryonic day 11 was separated for western blot assay and co-immunoprecipitation. RESULTS AND CONCLUSION:(1)Cx43 and Isl1 were co-expressed in some mesenchymal cells on the ventral side of the foregut and dorsal wall of the pericardial cavity of mouse embryos at embryonic days 10-12;Isl1 positive cells increased while Cx43 positive cells increased.(2)Cx43 and β-catenin were co-expressed in the ventral part of the endoderm at embryonic days 10-12.(3)Cx43 and Smo were co-expressed in the endoderm at embryonic days 10-12.(4)The co-immunoprecipitation results confirmed that there was an interaction between Cx43 and β-catenin,which suggested that Cx43 interacted with β-catenin to participate in the development of the second heart field.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To analyze the outcomes of catheter ablation for persistent atrial fibrillation(AF)and the independent risk factors for its recurrence in the elderly.Methods A total of 194 patients with persistent AF who underwent catheter ablation at our department from January 2019 to December 2021 were enrolled in this study.They were divided into elderly group(≥60 years old,99 cases)and non-elderly group(＜60 years old,95 cases).Their surgical characteris-tics,postoperative complications and recurrence were compared between the two groups,and the independent risk factors for postoperative recurrence were analyzed in the elderly group.Results Advanced age,higher B-type natriuretic peptide,larger proportions of hypertension and coronary heart disease,and increased CHA2DS2-VASc and HAS-BLED scores,while lower male ratio and estimated glomerular filtration rate were observed in the elderly group than the non-elderly group(P＜0.05,P＜0.01).The elderly group had a higher proportion of left atrial fibrosis than the non-elderly group(30.3％vs 8.4％,P=0.001).Postoperative complications in the elderly group in-cluded 1 case of pericardial effusion and 2 cases of hematoma at the puncture site,and all of these were improved after treatment.There were no significant differences in the 1-year success rate(71.7％vs 69.5％,P=0.763)or recurrence rate during blanking period(21.2％vs 21.1％,P=0.981)between the elderly and non-elderly groups.AF duration(HR=1.020,95％CI:1.007-1.032,P=0.002)and recurrence during blanking period(HR=6.781,95％CI:3.078-14.935,P=0.001)were independent risk factors for postoperative recurrence in the elderly group.Conclu-sion Catheter ablation is safe and effective in the treatment of persistent AF in the elderly.The elderly patients with long duration of AF and recurrences during blanking period are more likely to experience recurrences within 1 year after ablation.

Objective:To compare the short-term efficacy and the safety of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of benign thyroid nodules (BTNs).Methods:This prospective randomized controlled trial, performed from December 2019 to September 2021, included 36 patients with solid or predominantly solid BTNs who met the eligibility criteria and provided written informed consent at the Nanjing sub-center (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine). Patients were assigned to either the MWA group or the RFA group (18 patients in each group) at a ratio of 1∶1 using a block randomization design and allocation concealment using sealed envelope randomization. The independent-sample t-test and χ2 test were used to compare the volume reduction rates (VRRs), effective rates (VRRs≥50%), cosmetic scores, and complication rates at 1, 3, and 6 months after treatment between the two groups. Results:The clinical characteristics of the two groups of patients were comparable. After ablation, the nodule volume was significantly reduced in both groups. At 1, 3, and 6 months, there was no significant difference in the volume between the two groups (all P>0.05). At 3 months, the RFA group had a larger VRRs than that in the MWA group (62.08%±12.46% vs. 46.90%±23.16%, t=-2.45, P=0.021). However, at 1 and 6 months, no statistical significance was observed (both P>0.05). No significant difference was observed in the effective rates at the last follow-up (14/18 vs. 18/18, P=0.104). However, the RFA group had a lower cosmetic score than that in the MWA group (1.78±0.43 vs. 2.17±0.51, t=-2.47, P=0.019). There was no statistically significant difference in the complication rates between the two groups (all P>0.05). Conclusions:Both MWA and RFA were effective and safe treatments for BTNs, with no significant differences in short-term efficacy and safety. In addition, the RFA group showed slightly more favorable outcomes than the MWA group in terms of cosmetic improvement.

Objective This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting,clarifies and explores the quality control and supervision model for bioprinting medical devices,and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices.Methods The quality control risk points throughout the bioprinting process were comprehensively analyzed,with a particular focus on bioprinting materials and key processes.The regulatory model and methods for bioprinting medical devices were examined.This research concentrated on critical technologies such as extrusion,laser-assisted,and in situ bioprinting,assessing their potential for clinical applications and regulatory challenges.Results Bioink from different sources should meet regulatory requirements.It is essential to ensure aseptic handling of raw materials and to validate sterilization under"worst-case"conditions.Conclusion As bioprinting technology advances rapidly,corresponding research into materials,processes,and quality risk control should be conducted to ensure the concurrent development of the regulatory system.This will continuously contribute to the orderly progression of the entire industry and human health.

Objective To investigate the role of hsa_circ_0011946 targeting miR-767-3p in the progression of cervical cancer.Methods The expression levels of hsa_circ_0011946 and miR-767-3p in cervical cancer tissues,adjacent tissues,immortalized human cervical epithelial cells(H8)and cervical cancer cells(SiHa,HeLa,and Cashi)were determined by RT-qPCR.SiHa cells were transfected with si-NC,si-hsa_circ_0011946,miR-NC,miR-767-3p,pcDNA,pcDNA-hsa_circ_0011946,anti-miR-NC+si-hsa_circ_0011946,anti-miR-767-3p+ si-hsa_circ_0011946,respectively,as the si-NC group,the si-hsa_circ_0011946 group,the miR-NC group,the miR-767-3p group,the pcDNA group,the pcDNA-hsa_circ_0011946 group,the anti-miR-NC+si-hsa_circ_0011946 group,and the anti-miR-767-3p+si-hsa_circ_0011946 group,and the untransfected cells were used as the NC group.The expression of hsa_circ_0011946 and miR-767-3p of SiHa cells in each group was detected by RT-qPCR,the cell viability was detected by CCK-8,the number of cell clone was detected by plate clone formation assay,the cell migration and invasion numbers were detected by Transwell assay,and the protein expression of MMP-2 and MMP-9 was detected by Western blot.The binding site of miR-767-3p to hsa_circ_0011946 was predicted by circular RNA interactome,and the targeted relationship between hsa_circ_0011946 and miR-767-3p was analyzed by dual luciferase reporter assay.Results Compared with the adjacent tissues,the expression level of hsa_circ_0011946 in the cervical cancer tissues was significantly increased(P<0.05),while the expression level of miR-767-3p was significantly decreased(P<0.05).Compared with H8 cells,the expression levels of hsa_circ_0011946 in SiHa,HeLa and Caski cells were significantly increased(P<0.05),while the expression levels of miR-767-3p were signifi-cantly decreased(P<0.05).Compared with the NC group,the expression level of hsa_circ_0011946,absorbance(A)value,number of clone,number of migration,number of invasion and the protein expression levels of MMP-2 and MMP-9 were significantly decreased in SiHa cells in the miR-767-3p group(P<0.05).Compared with the miR-NC group,the expression level of miR-767-3p in SiHa cells in the miR-767-3p group was significantly increased(P<0.05),and the cell A value,number of clone,number of migration,number of invasion and the protein expression levels of MMP-2 and MMP-9 were significantly decreased(P<0.05).Compared with the pcDNA group,the expression level of miR-767-3p in SiHa cells in the pcDNA-hsa_circ_0011946 group was significantly decreased(P<0.05),and the expression level of hsa_circ_0011946 was significantly increased(P<0.05).The relative luciferase activity of SiHa cells co-transfected with miR-767-3p mimics and WT-hsa_circ_0011946 was lower than that of co-transfected with miR-NC and WT-hsa_circ_0011946(P<0.05).hsa_circ_0011946 bound to miR-767-3p directly and specifically.Compared with the anti-miR-NC+si-hsa_circ_0011946 group,the expression level of miR-767-3p in SiHa cells in the anti-miR-767-3p+si-hsa_circ_0011946 group was significantly decreased(P<0.05),and the cell A value,number of clone,number of migration,number of invasion and protein expression levels of MMP-2 and MMP-9 were significantly increased(P<0.05).Conclusion Interfering hsa_circ_0011946 can inhibit the proliferation,migration and invasion of cervical cancer cells through targeted up-regulation of miR-767-3p.

OBJECTIVE To predict the possible impact of pembrolizumab（PEM） as a first-line drug after being included in the national medical insurance system in the treatment of advanced or metastatic non-small cell lung cancer based on real-world data from the perspective of the national medical insurance payer， to provide a basis for the decision-making of the medical insurance department. METHODS A budget impact analysis model was constructed to compare the impact of pembrolizumab not included in medical insurance and included in medical insurance on medical insurance fund expenditure in the next five years（ 2024- 2028） with 2023 as the baseline year. The target population was the patients with EGFR gene mutation-negative and anaplastic lymphoma kinase （ALK）-negative locally advanced or metastatic non-small cell lung cancer； estimated cost mainly included the cost of drugs， the cost of adverse reaction treatment， the cost of examination， the cost of admission and monitoring， etc； equipment ratio of PEM in 183 hospitals of Guangdong province from 2020 to 2022 was used as the market share. Univariate sensitivity analysis was used to test the robustness of the basic analysis results. RESULTS When PEM was not included in the medical insurance， the medical insurance reimbursement amount of the target population from 2024 to 2028 was 4 933 623.5 thousand yuan-5 151 198.3 thousand yuan， respectively. If PEM was included in the medical insurance， the above data were 11 871 972.2 thousand yuan-14 540 571.0 thousand yuan， respectively； the increase in medical insurance reimbursement under the two scenarios was 6 720 773.9 thousand yuan-9 606 947.5 thousand yuan， respectively. The proportion of medical insurance reimbursement to the medical insurance expenditure of the year after PEM was included in medical insurance was 0.298 0%， 0.262 1%， 0.228 8%， 0.208 2%， and 0.185 7%， respectively. The increase in medical insurance reimbursement accounted for 1.084 0%， 0.995 7%， 0.888 6%， 0.886 3%， and 0.861 6% of the increase in the expenditure of the medical insurance fund in the current year， all of which showed a decreasing trend year by year. CONCLUSIONS If PEM is included in medical insurance， due to its high unit price， the medical expenditure will increase accordingly， which will have a great impact on the medical insurance fund expenditure. However， when the drug is used in patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic non-small cell lung cancer， the proportion of the medical insurance reimbursement amount in the current year’s medical insurance fund expenditure and the proportion of the increase in medical insurance reimbursement in the current year’s increase in medical insurance fund expenditure are decreasing year by year.

WRKY transcription factor is a type of transcription factor unique to plants and plays an important role in various physiological processes of plants. This study is based on the transcriptome data of Atractylodes lancea, the correlation between the FPKM values of the AlWRKY gene and the AlTPS gene of Atractylodes lancea was analyzed. Combined with the analysis results, the candidate gene AlWRKY65 with a significant positive correlation with the expression levels of AlTPS1 and AlTPS6 genes and a relatively high FPKM value was screened. The candidate gene was cloned to obtain the open reading frame ORF of the AlWRKY65 gene, and the related information of its encoded protein was analyzed and the gene expression was studied. The results showed that AlWRKY65 contains a 681 bp open reading frame and encoding 226 amino acids. Through amino acid sequence homology analysis, it was found that AlWRKY65 amino acid sequence had high homology with several plants such as HaWRKY65 and LsWRKY65; AlWRKY65 protein had a typical WRKYGQK domain, belonging to IIe subgroup of WRKY transcription factor family; phylogenetic analysis indicated that AlWRKY65 protein had the higher homology with CcWRKY65 protein; the expression of AlWRKY65 gene in different tissues of two producing areas of Atractylodes lancea were assayed via real-time fluorescence quantitative PCR, and the results showed that all of them were highly expressed in leaves and also has tissue differences. The expression level of AlWRKY65 gene was down-regulated within 48 h of methyl jasmonate (MeJA) induction; subcellular localization and transcriptional activation assay suggested that AlWRKY65 was located in the nucleus and had no transcriptional activation activity. This study provides a reference for further elucidating the biological function of AlWRKY65 in Atractylodes lancea.