Objective To investigate the role of transcription factor EB(TFEB)in endotoxin-tolerant macrophages.Methods The RAW264.7 cells were divided into blank group(DMEM medium),LPS 5 group(5 ng/mL LPS treatment for 4 h),LPS 100 group(100 ng/mL LPS treatment for 4 h),and tolerance group(5 ng/mL LPS for 12 h followed by 100 ng/mL LPS for 4 h).The releases of inflammatory factors TNF-α and IL-6 were measured using ELISA.Western blotting and immunofluorescence assay were used to evaluate the distribution of autophagy-related proteins LC3 and P62,as well as TFEB in the cytoplasm and nucleus.Lentiviral overexpression of TFEB or siRNA-mediated knockdown of TFEB were performed to observe the changes in autophagy levels and bacterial clearance ability in the tolerant cells.Results The cells in the tolerance group had significantly lower contents of TNF-α and IL-6,as well as reduced bacterial clearance ability(P<0.01),down-regulated LC3 expression while up-regulated P62 level,and decreased expression of TFEB in both the cytoplasm and nucleus(P<0.01)when compared with the cells of the LPS 100 group.Overexpression of TFEB significantly increased LC3 level,reduced P62 level,and enhanced bacterial clearance ability in the endotoxin-tolerant cells(P<0.01).In contrast,siRNA-mediated knockdown of TFEB had no significant impacts on LC3 and P62 expression levels or bacterial clearance ability.Conclusion Overexpression of TFEB can restore the autophagy of endotoxin-tolerant cells and enhance their bacterial clearance capacity,thereby alleviating the immunosuppressive state of sepsis.These findings suggest that TFEB holds promise as a potential therapeutic target for the prevention and treatment of sepsis.

Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate the protective effect and mechanism of Danshen Tongluo Jiedu Decoction medicated serum for hypoxia/reoxygenation rat myocardial microvascular endothelial cells(CMECs)by regulating MALAT1.Methods Rats CMECs cells were cultured in vitro to establish a model of hypoxia/reoxygenation damaged cells,and were transfected overexpressing/silencing blank MALAT1 slow virus,cells were divided into overexpressed blank + TCM group,overexpressed MALAT1 + TCM group,overexpressed MALAT1 group,silenced blank + TCM group,silenced MALAT1 group,and silenced MALAT1 + TCM group.They were cultured with corresponding serum separately.Beclin-1 protein expression was detected by immunofluorescence method,and SRPK1,SRSF1,VEGF and Bax protein expressions were detected by Western blot,MALAT1,SRPK1 and SRSF1 mRNA expressions were detected by RT-PCR.Results Compared with the overexpressed blank + TCM group,Beclin-1 protein expression increased in the overexpressed MALAT1 + TCM group,the protein expressions of SRPK1,SRSF1 and Bax significantly increased(P<0.05,P<0.01),VEGF protein expression significantly decreased(P<0.01),while MALAT1,SRPK1 and SRSF1 mRNA expressions significantly increased(P<0.05,P<0.01).Compared with the overexpressed MALAT1 group,the protein expression of Beclin-1 in overexpressed MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01,P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.05).Compared with the silenced blank + TCM group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01),while the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01).Compared with the silenced MALAT1 group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01,P<0.05).Conclusion Upregulation of MALAT1 expression can promote autophagy in hypoxia/reoxygenation model CMECs,while Danshen Tongluo Jiedu Decoction medicated serum can inhibit MALAT1 expression,thus inhibiting autophagy and promoting angiogenesis,and the mechanism may be related to the downregulation of SRPK1 and SRSF1 expressions.

Objective:To investigate the characteristics of attention bias to aggressive information under self-threat priming in college students with different types of high self-esteem.Methods:A total of 650 college students were selected,and high self-esteem participants were selected through the Self Esteem Scale(SES).Then,43 partic-ipants were selected from different types of high self-esteem(fragile and safe)groups through the Implicit Associa-tion Test(IAT).Each group participated in Raven's Standard Progressive Matrices(SPM)with different difficulty levels to complete self-threat priming,and then completed the spatial cue experiment.When the cue was invalid,the attention bias was obtained according to the variation of the reaction time difference(RTI)between the subjects're-sponses to aggressive words and neutral words.Results:The RTI values of the fragile high self-esteem group were higher under high self-threat priming than that of the secure high self-esteem group(P＜0.01).Under low self-threat priming,there was no significant difference in RTI values among different types of high self-esteem groups(P＞0.05).Conclusion:Fragile high self-esteem group are more likely to develop attention bias towards aggressive words under high self-threat priming than that of secure high self-esteem group.

Objective To explore the application effect of healthcare failure mode and effect analysis (HFMEA) in nursing risk management of emergency surgery for patients with traumatic brain injury (TBI). Methods Taking the HFMEA model as the theoretical framework, the emergency surgical process of TBI was analyzed, a flow chart was drawn, and the potential risk factors were analyzed. Corresponding intervention programs were adopted for high-risk failure modes, and 80 patients from November 2022 to April 2023 were conducted with routine management before implementation of HFMEA (control group), the other 80 patients from May to October 2023 were conducted with management after implementation of HFMEA (observation group). The surgical efficiency (preoperative waiting time, surgical preparation time, anesthesia induction time, postoperative handover time), the incidence rates of adverse events in the operation room (incomplete preparation of supplies, contamination of surgical drapes, insufficient or defective intraoperative instruments, errors in writing nursing records, incorrect or missing items in handover information), the incidence rates of perioperative complications (low intraoperative body temperature, pressure injury, abnormal fluctuations in vital signs during surgery, wound infection, lung infection) and satisfaction degree of surgical doctors to nurses for current operations (itinerant nurses, instrument nurses) were compared between two groups. Results The observation group had significantly shorter preoperative waiting time, surgical preparation time, anesthesia induction time, and postoperative handover time compared to the control group (P < 0.01). The incidence rate of adverse events in the operation room for the observation group was 16.25%, which was significantly lower than 46.25% of the control group (P < 0.01). The incidence rate of complications was 8.75% in the observation group, which was significantly lower than 26.25% in the control group (P < 0.01). Satisfaction degree of the doctors to nurses for the current operation in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion Application of the HFMEA model in the perioperative nursing management of patients with emergency surgery for TBI can effectively improve surgical efficiency, reduce the incidence rates of nursing-related adverse events and complications, and enhance satisfaction degree of doctors to nurses in operation room.

The acute myeloid leukemia and myelodysplastic syndromes are common myeloid neoplasms for which allogeneic hematopoietic stem cell transplantation is one of the main curative therapies. In high-risk patients, the relapse rate can be more than 40%, and patients with post-transplantation relapses have a very poor prognosis, so preventing relapse after transplantation is crucial. The maintenance therapy is a group of interventions to prevent relapse when morphological, molecular biological and cytogenetic results are constantly negative after transplantation. Currently, the commonly used maintenance therapy is the application of demethylating drugs, targeted drugs, etc., but their necessity, medicine plan, adverse effects, multi-drug combinations, and other aspects need to be studied urgently. This article will systematically describe the progress of post-transplantation maintenance therapy for high-risk myeloid neoplasms based on drug classification.

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV₁%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV₁%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

Background/Aims: Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods: We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results: Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.

To investigate the values of orbital single photon emission computed tomography/computerized tomography (SPECT/CT) with 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) on the evaluation of lacrimal gland inflammation in patients with thyroid associated ophthalmopathy (TAO).
 Methods: A total of 58 TAO patients were retrospectively recruited for this study, all of whom were categorized into all active group and all inactive group based on the clinical active score (CAS). Another 12 patients with the negative images on SPECT/CT served as a normal control group (NC). All patients were undergone the 99mTc-DTPA orbit SPECT/CT. Quantitative parameters of lacrimal gland including width, length, volume, and the count ratio of region of interest (ROI) drawn on lacrimal gland to the region of occipital brain (target/non-target ratio, T/NT), were measured on axial and coronal slices, respectively. Quantitative parameters were compared among the 3 groups, and the diagnostic value on discrimination of TAO patients from inactive to active ones was evaluated.
 Results: All parameters in TAO patients (except the length on coronal slices and the mean radioactive counts of axial T/NT in the TAO inactive group) were much greater than those in the NC group (P<0.05). All parameters in the TAO active group (except the length on axial and coronal slices) were much greater than those in the TAO inactive group (P<0.05). There were significant lineal positive correlations between the parameters in all TAO patients (except the length on coronal slices ) and CAS. The best diagnostic value was detected by the max radioactive counts of axial T/NT (area under the curve=0.82, P<0.01).
 Conclusion: As an invasive imaging modality, 99mTc-DTPA orbital SPECT/CT is helpful to estimate the lacrimal gland inflammation and to assess the disease activity in TAO patients.
Graves Ophthalmopathy ; Humans ; Inflammation ; Lacrimal Apparatus ; Orbit ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed