Objective:To investigate the correlation between serum neuron-specific enolase (NSE) levels and poor neurological outcomes in cardiac arrest (CA) patients supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods:This retrospective analysis was conducted on adult CA patients treated with VA-ECMO at Hangzhou First People's Hospital Affiliated to Westlake University School of Medicine, and Second Affiliated Hospital Zhejiang University School of Medicine, from December 2018 to February 2024. General clinical data and serial serum NSE levels at 24, 48, and 72 h after ECMO initiation were collected. Based on the Glasgow-Pittsburgh Cerebral Performance Category (CPC) at discharge, patients were divided into poor neurological outcome group (CPC 3-5) and good neurological outcome group (CPC 1-2). Differences in serum NSE levels between the two groups were compared. The accuracy of serum NSE levels at three time points in predicting poor neurological outcomes in CA patients was assessed via receiver operating characteristic curves, and the optimal cut-off values were determined by the Youden index. Multivariate logistic regression analysis was performed to determine the relationship between serum NSE levels and poor neurological outcomes. Subgroup analysis was based on age, sex, location of CA, and extracorporeal cardiopulmonary resuscitation (ECPR).Results:A total of 120 eligible CA patients were included, with 88 patients (73.3%) having poor neurological outcomes at discharge. Serum NSE levels at 24, 48, and 72 h after ECMO initiation were higher in the poor outcome group compared to the good outcome group (all P<0.05). The serum NSE level at 72 h had the highest accuracy in predicting poor outcomes, with an area under the curve (AUC) of 0.91 (95% CI: 0.85-0.96), and a cut-off value of 42.0 μg/L. The AUCs for 24 and 48 h were 0.78 (95% CI: 0.69-0.86) and 0.87 (95% CI: 0.80-0.94), with cut-off values of 70.6 μg/L and 64.5 μg/L, respectively. Multivariate logistic regression analysis suggested that the serum NSE level at 72 h was associated with poor outcomes ( P<0.05), and an NSE level >42.0 μg/L was an independent risk factor for poor outcomes ( OR=20.29, 95% CI: 2.90-92.15). Subgroup analysis showed that serum NSE level at 72 h was an independent risk factor for poor neurological outcomes in CA patients aged<60 years old, male or female, out-of-hospital or in-hospital CA, and whether to perform ECPR (all P<0.05). Conclusion:Elevated serum NSE levels at 72 h after VA-ECMO initiation are associated with poor neurological outcomes in CA patients, with the cut-off value of 42.0 μg/L.

Objective To analyze anesthetic and analgesic effect of perioperovtive administration of esketamine in patients undergoing off-pump coronary artery bypass grafting(OPCABG).Methods The clinical data of 120 patients who underwent OPCABG under gene-ral anesthesia were retrospectively collected.Patients were divided into an esketamine group(n=60)and a non-esketamine group(n=60)according to whether esketamine was used perioperatively.The patients in the esketamine group received esketamine(1 mg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg)plus esketamine(2 mg/kg).Those in the non-esketamine group received sufentanil(2 μg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg).The mean arterial pressure(MAP)and heart rate(HR)were recorded at the time point of entering the room(T0),after anesthesia induction/before intubation(T1),1 min after intubation(T2),skin incision(T3),sternotomy(T4),after surgery and skin suture(T5),entering the ICU(T6),extubation(T7),24 hours after surgery(T8),and 48 hours after surgery(T9).The extubation time,Ramsay sedation scores,visual analog scale(VAS)scores,and adverse reactions were compared.Results There were no statistically significant differences in the baseline characteristics and MAP and HR at T0 and T1 between the two groups(P＞0.05).From T2 to T9,MAP and HR in the esketamine group were significantly lower than those in the non-esketamine group(P＜0.05).The postoperative extubation time,Ramsay sedation score,and VAS score were significantly lower in the esketamine group than in the non-esketamine group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The perio-perative administration of esketamine in OPCABG can stabilize the hemodynamics,shorten the extubation time,and promote the recovery of patients undergoing OPCABG without increasing postoperative adverse reactions.

Objective To analyze anesthetic and analgesic effect of perioperovtive administration of esketamine in patients undergoing off-pump coronary artery bypass grafting(OPCABG).Methods The clinical data of 120 patients who underwent OPCABG under gene-ral anesthesia were retrospectively collected.Patients were divided into an esketamine group(n=60)and a non-esketamine group(n=60)according to whether esketamine was used perioperatively.The patients in the esketamine group received esketamine(1 mg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg)plus esketamine(2 mg/kg).Those in the non-esketamine group received sufentanil(2 μg/kg)during anesthesia induction and postoperative patient-controlled analgesia with sufentanil(3 μg/kg).The mean arterial pressure(MAP)and heart rate(HR)were recorded at the time point of entering the room(T0),after anesthesia induction/before intubation(T1),1 min after intubation(T2),skin incision(T3),sternotomy(T4),after surgery and skin suture(T5),entering the ICU(T6),extubation(T7),24 hours after surgery(T8),and 48 hours after surgery(T9).The extubation time,Ramsay sedation scores,visual analog scale(VAS)scores,and adverse reactions were compared.Results There were no statistically significant differences in the baseline characteristics and MAP and HR at T0 and T1 between the two groups(P＞0.05).From T2 to T9,MAP and HR in the esketamine group were significantly lower than those in the non-esketamine group(P＜0.05).The postoperative extubation time,Ramsay sedation score,and VAS score were significantly lower in the esketamine group than in the non-esketamine group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The perio-perative administration of esketamine in OPCABG can stabilize the hemodynamics,shorten the extubation time,and promote the recovery of patients undergoing OPCABG without increasing postoperative adverse reactions.

Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disease that affects multiple organs.Extracel-lular vesicles(EVs),including exosomes,microparticles and apoptotic bodies,are released by most types of cells and carry nucleic acids,proteins and lipids,which play a crucial role in communication among cells.In SLE,extracellular vesicles can act as autoadju-vants to enhance the formation of immune complexes and maintain inflammatory states.In this review,the biological origin and mes-senger role of EVs in cell communication are reviewed,and the research progress of EVs in immune regulation and pathogenesis in SLE is highlighted.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

OBJECTIVE: Compared with the method of optical microscopy, to evaluate the accuracy of fragmented red cells(FRC) detection by Sysmex XN-3000. METHODS: A total of 111 samples were collected from patients diagnosed as thrombotic thrombocytopenic purpura, autoimmune disease, hematological disease, malignant tumor and health examination in our hospital from June 2019 to February 2021, including 74 cases in the case group and 37 cases in the healthy control group. All samples were detected by optical microscope and Sysmex XN-3000, respectively. ROC was used to evaluate the detection ability of Sysmex XN-3000 for schistocyte. Bland-Altman method was used to evaluate the consistency of the results of the two methods for detection of schistocyte, and Pearson correlation analysis was conducted for the difference of the results. RESULTS: The area under the ROC curve was 0.890(95% CI: 0.828-0.952, P<0.01). Sysmex XN-3000 count did not quantitatively agree with schistocyte counts by microscopy in the case group(mean of difference:-1.53, 95% limits of agreement: -8.78~5.72). There was a weak positive correlation between platelet count and the difference of analyzer and microscopic results (r=0.32,P<0.05). CONCLUSION Sysmex XN-3000 can be used as a reference for qualitative determination of schistocyte. However, the sensitivity of Sysmex XN-3000 should be improved. It is still necessary to combine with manual microscopy. The quantitative results are not reliable now and cannot be used as a reference for monitoring the results of schistocyte in clinical patients after treatment.
Humans ; Neoplasms ; Platelet Count ; Purpura, Thrombotic Thrombocytopenic ; ROC Curve ; Reproducibility of Results

WRKY, a class of conserved transcription factors in plants, plays important roles in plant growth, development and secondary metabolism. In the present study, 65 WRKY members were identified from de novo transcriptome sequencing data of three different tissues (root, stems and leaves) of Baphicacanthus cusia. BcWRKY proteins contained from 221 to 706 amino acids and the isoelectric point is from 4.68 to 9.68. Molecular weights range from 25 711.8 to 75 475 Da. The main secondary structures of BcWRKYs protein are random coil. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Phylogenetic analysis showed that BcWRKYs could be categorized into three groups and five subgroups (Group IIa, Group IIb, Group IIc, Group IId and Group IIe) in Group II. Structural analysis found that all BcWRKY proteins contained a highly conserved motif WRKYGQK. Finally, the transcriptional profiles of ten BcWRKY genes highly expressed in root, stem and leaf tissues under abscisic acid (ABA), methyl jasmonate (MeJA), or salicylic acid (SA) treatment were systematically investigated using qRT-PCR analysis. Results showed that a total of ten BcWRKY genes were differentially expressed in response to ABA, MeJA, and SA treatment. This work would be provided a basis for further elucidating the molecular mechanism of WRKY transcription factors in the biosynthesis of indole alkaloids in B. cusia.

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.
Carcinoma, Squamous Cell/therapy* ; Chemoradiotherapy ; Humans ; Quality of Life ; Retrospective Studies ; Tonsillar Neoplasms/therapy*

Pulmonary hypertension ( PH) is occult, with no distinctive clinical manifestations and poor prognosis.Pulmonary vascular remodelling is an important pathological feature in which pulmonary artery smooth muscle cell ( PASMCs) pheno- typic switching plays a crucial role.MicroRNA (miRNA) is a class of evolutionary highly conserved single-stranded small non-coding RNA.Recently, an increasing number of scholars have found that miRNA can play an important role in the occurrence and development of PH by regulating the phenotypic switching of PASMCs, which is expected to be a potential target for the prevention and treatment of PH.It has been found that miR NA such as miR-221 , miR-24, miR-15b, miR-96, miR-23a.miR-9, miR-214, miR-20a can promote the phenotypic switching of PASMCs, while miRNA such as miR-21, miR-132, miR-182, miR-449, miR-206 .miR-124, miR-30c, miR-140.miR-17-92 cluster can inhibit it.This article aims to review the research progress on miRNA that mediates PASMCs phenotypic switching in PH from both growth factor-related miRNA and hy- poxia-related miRNA.

OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/genetics* ; Apoptosis ; Signal Transduction ; Proto-Oncogene Proteins c-bcl-2 ; Granulosa Cells ; Mice, Transgenic ; Mice, Knockout ; TOR Serine-Threonine Kinases