ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Plants of the Isodon genus are an important source of terpenoids， with their constituents exhibiting rich structural diversity and remarkable biological activities （such as anticancer， antimicrobial， and anti-inflammatory properties）， demonstrating significant potential in the field of immunomodulation. This review summarizes recent advances in the immunomodulatory mechanisms， development and application of terpenoid compounds from the Isodon genus. It has been found that these compounds can modulate key inflammatory signaling pathways， such as nuclear factor-kappa B （NF-κB） and mitogen-activated protein kinases （MAPKs）， thereby blocking the cascade amplification of inflammatory factors， alleviating chronic inflammatory responses， and correcting immune dysregulation. Additionally， they can influence the polarization direction of macrophages and dynamically regulate the balance among different functional subsets of T cells， restoring immune homeostasis. Their clinical translation faces multiple challenges， including poor druggability， a lack of systematic safety data， the absence of precise pharmacodynamic biomarkers， complexities in clinical trial design， and unclear industrialization pathways.

Objective To investigate the diagnostic value of combined clinical imaging model in deep infiltrating endometriosis of uterosacral ligaments(USL-DIE).Methods The preoperative clinical symptoms,signs,transvaginal ultrasound(TVS)and MRI diagno-ses of 102 DIE patients were reviewed and subjected to univariate analysis,and the significant variables were screened and included in the multivariable logistic regression analysis to construct a combined clinical imaging model.The diagnostic value of statistically signifi-cant factors and combined model was assessed and compared using receiver operating characteristic(ROC)curve.Results The inci-dence of USL nodule with tenderness,the detection rates of TVS and MRI for USL-DIE were higher than those of other patients with DIE,and the differences were statistically significant.TVS(P=0.021)and MRI(P<0.001)were independent factors in the diag-nosis of USL-DIE.The combined clinical imaging model had the highest area under the curve(AUC)(0.909)and specificity(0.929)for the diagnosis of USL-DIE.Conclusion The combined clinical imaging model has a higher value for the comprehensive diagnosis of USL-DIE compared with clinical or imaging diagnosis alone.

Objective To investigate the diagnostic value of combined clinical imaging model in deep infiltrating endometriosis of uterosacral ligaments(USL-DIE).Methods The preoperative clinical symptoms,signs,transvaginal ultrasound(TVS)and MRI diagno-ses of 102 DIE patients were reviewed and subjected to univariate analysis,and the significant variables were screened and included in the multivariable logistic regression analysis to construct a combined clinical imaging model.The diagnostic value of statistically signifi-cant factors and combined model was assessed and compared using receiver operating characteristic(ROC)curve.Results The inci-dence of USL nodule with tenderness,the detection rates of TVS and MRI for USL-DIE were higher than those of other patients with DIE,and the differences were statistically significant.TVS(P=0.021)and MRI(P<0.001)were independent factors in the diag-nosis of USL-DIE.The combined clinical imaging model had the highest area under the curve(AUC)(0.909)and specificity(0.929)for the diagnosis of USL-DIE.Conclusion The combined clinical imaging model has a higher value for the comprehensive diagnosis of USL-DIE compared with clinical or imaging diagnosis alone.

Objective To compare the diagnostic value of transvaginal ultrasound(TVS)and thin-section oblique axial T2WI in deep infiltrating endometriosis(DIE)of uterosacral ligaments(USL).Methods Retrospective analysis was conducted on preoperative TVS and MRI images from 74 patients with USL-DIE.The diagnostic efficacy of TVS and thin-section oblique axial T2WI for USL-DIE was evaluated using receiver operating characteristic(ROC)curve based on pathological findings,and area under the curve(AUC),sensitivity,specificity,accuracy,positive predictive value(PPV)and negative predictive value(NPV)were further calculated.The McNemar two-tailed test was used to analyze the difference in diagnostic accuracy between the two methods for USL-DIE.Results The AUCs of TVS and thin-section oblique axial T2WI for diagnosing left and right USL-DIE were 0.721 vs 0.842 and 0.640 vs 0.901,respectively.Thin-section oblique axial T2WI demonstrated higher sensitivity,accuracy,PPV,and NPV compared to TVS in diagnosing USL-DIE.The diagnostic accuracy was found to be statistically different between the two methods(Pleft =0.026,χ2=4.966;Pright<0.001,χ2=16.531).Conclusion Thin-section oblique axial T2WI outperformed TVS in terms of diagnostic value for USL-DIE,providing valuable imaging support for accurate clinical diagnosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background Due to the prominent particularity of medical work,nurses are prone to developing depression,which not only poses a considerable threat to the physical and mental health of nurses,but also affects the quality of nursing to some extent.Occupational stress is a known contributor to depression in nurses,whereas relatively little research has been done to investigate the underlying mediation path.Objective To explore the mediation effect of perceived organizational support and psychological capital on the relationship between occupational stress and depression among nurses,and to provide theoretical references for the prevention and treatment of occupational stress-induced depression in nurses.Methods From March to August 2019,a stratified random sampling method was utilized to select a sample size of 720 nurses in each department of a grade A tertiary hospital in Shandong Province.All subjects were assessed using Effort-Reward Imbalance Questionnaire(ERI),Perceived Organization Support Questionnaire(POS),Psychological Capital Questionnaire(PCQ)and Center for Epidemiologic Studies Depression Scale(CES-D).Pearson correlation was adopted to examine the correlation among above scales,and multilevel mediation analyses were conducted with model 6 in Process macro(version 3.3)for SPSS 26.0 using Bootstrap re-sampling method.Results A total of 658 nurses(91.39%)completed the effective questionnaire survey.ERI score was positively correlated with CES-D score(r=0.499,P<0.01),and negatively correlated with POS and PCQ scores(r=-0.318,-0.275,P<0.01).POS score was positively correlated with PCQ score(r=0.455,P<0.01),and negatively correlated with CES-D score(r=-0.401,P<0.01).PCQ score was negatively correlated with CES-D score(r=-0.567,P<0.01).The total effect value of occupational stress on depression was 0.466(95%CI:0.399～0.534).Perceived organizational support(indirect effect value of 0.027,95%CI:0.006～0.057)and psychological capital(indirect effect value of 0.059,95%CI:0.013～0.120),separately from each other,mediated the relationship between occupational stress and depression,and a chained mediation effect of perceived organizational support and psychological capital was also demonstrated(indirect effect value of 0.051,95%CI:0.031～0.082),accounting for 10.94%of the total effect.Conclusion Occupational stress is a influencing factor of nurses' depression,which can affect the occurrence of depression both directly and indirectly through either separate or chained mediation of perceived organizational support and psychological capital.

Humans ; Gemcitabine ; Neoplasms

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis