Reasonable and standardised placebo setting for acupoint application pastes is a key factor for clinical trials to verify the safety and effectiveness of acupoint application. By sorting out the current design status of placebo in the allocation concealment and blind design， paste components， paste location， paste duration in the current clinical trials of acupoint application pastes， it is proposed that there are problems such as low application rate of blinding and non-standardised reporting， insufficient standardisation of placebo settings and lack of systematic research， and lack of uniform standards of the placebo evaluation method. Based on the action mechanism of acupoint application， the idea of setting placebo for acupoint application paste is proposed in terms of replacing the application material， controlling the physicochemical effect produced by transdermal absorption of drugs， and setting the permeability of placebo， in order to enrich the methodological content of the placebo setting for acupoint application， and providing more scientific and reliable clinical evidence of acupoint application.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Objective To observe early changes of left atrial strain and left atrial stiffness index(LASI)in rabbits with left ventricular myocardial injury induced by adriamycin(ADM).Methods Eighteen New Zealand white rabbits were randomly divided into experimental group(n=12)and control group(n=6),while 2 mg/kg ADM was injected into rabbits in experimental group and 5 ml physiological saline was injected into rabbits in control group every week for a total of 4 weeks.Ultrasound examination was performed before injection of ADM/physiological saline,2 and 4 weeks after injection,respectively.Left atrial anteroposterior diameter(LAAPD),left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),lateral wall of mitral ring of early peak flow velocity(e),mitral valve orifice early peak flow velocity(E)/e,left ventricular global longitudinal strain(LVGLS),right ventricular collectivity long axis strain(RVCLS),left atrial strain during reservoir phase(LASr),left atrial strain during conduit phase(LAScd),left atrial strain during contraction phase(LASct)and LASI were obtained and analyzed.After ultrasound examination,myocardial changes were observed with pathological examination.Results Four weeks after injection,e in experimental group was significantly lower than that before injection,also lower than that 2 and 4 weeks after injection in control group(all P＜0.05).Significant differences of LASr,LAScd,LASct and LASI were found among different time points between groups(all P＜0.05).Two and 4 weeks after injection,the above 4 parameters in experimental group were all significantly different with those in control group(all P＜0.05).LASr,LASct and LASI were different among different time points,while LAScd before injection was higher than that 2 and 4 weeks after injection in experimental group(all P＜0.05).The pathological findings supported ultrasonic changes.Conclusion In early stage of ADM induced left ventricular myocardial injury in rabbits,changes of left atrial strain and LASI could be seen,which were more significant than those of LVGLS,RVCLS and LVEF,etc.

BackgroundSchool bullying is a serious social issue. Non-suicidal self-injury （NSSI） is a highly prevalent behavior among adolescents with depression and is also becoming a great matter of concern. Previous studies have proved a very close correlation among school bullying， experiential avoidance， family functioning， and NSSI behavior. However， there is a considerable lack of research on the moderating role of family functioning in the relationship between school bullying and experiential avoidance in adolescents with depression in China. ObjectiveTo explore the mediating role of experiential avoidance in the relationship between school bullying and NSSI in adolescents with depressive disorder， and the moderating role of family functioning in the relationship between school bullying and experiential avoidance， so as to provide references for formulating intervention strategies for NSSI in adolescents with depressive disorder. MethodsFrom January to December 2024， 318 consecutive adolescent patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for depression and attending the outpatient department of Weifang Mental Health Center were selected. All respondents completed the Delaware Bullying Victimization Scale-Student （DBVS-S）， Acceptance and Action Questionnaire-II （AAQ-II）， Family Assessment Device （FAD）， and Behavioral Questionnaire in the Adolescent Non-suicidal Self-injury Assessment Questionnaire （ANSAQ）. Pearson correlation was used to examine the relationship among variables. SPSS Process Macro v4.1 package program was utilized to seek the mediating and moderating effects. ResultsData were collected from 306 valid respondents （96.23%）. In adolescent with depressive disorder， DBVS-S score was positively correlated with both the behavioral questionnaire score in the ANSAQ and the AAQ-II score （r=0.357， 0.558， P<0.01）. AAQ-II score was positively correlated with the behavioral questionnaire score in the ANSAQ （r=0.380， P<0.01）. Experiential avoidance partially mediated the relationship between school bullying and NSSI in adolescents with depressive disorder， and the mediating effect value was 0.142 （95% CI： 0.081~0.204）. Family functioning moderated the relationship between school bullying and experiential avoidance， and the moderated mediation value was 0.096 （95% CI： 0.042~0.165）. ConclusionMediation is found from school bullying to NSSI behavior through experiential avoidance in adolescents with depressive disorder， and family functioning plays a moderating role in the relationship between school bullying and experiential avoidance.

Objective To observe early changes of left atrial strain and left atrial stiffness index(LASI)in rabbits with left ventricular myocardial injury induced by adriamycin(ADM).Methods Eighteen New Zealand white rabbits were randomly divided into experimental group(n=12)and control group(n=6),while 2 mg/kg ADM was injected into rabbits in experimental group and 5 ml physiological saline was injected into rabbits in control group every week for a total of 4 weeks.Ultrasound examination was performed before injection of ADM/physiological saline,2 and 4 weeks after injection,respectively.Left atrial anteroposterior diameter(LAAPD),left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),lateral wall of mitral ring of early peak flow velocity(e),mitral valve orifice early peak flow velocity(E)/e,left ventricular global longitudinal strain(LVGLS),right ventricular collectivity long axis strain(RVCLS),left atrial strain during reservoir phase(LASr),left atrial strain during conduit phase(LAScd),left atrial strain during contraction phase(LASct)and LASI were obtained and analyzed.After ultrasound examination,myocardial changes were observed with pathological examination.Results Four weeks after injection,e in experimental group was significantly lower than that before injection,also lower than that 2 and 4 weeks after injection in control group(all P＜0.05).Significant differences of LASr,LAScd,LASct and LASI were found among different time points between groups(all P＜0.05).Two and 4 weeks after injection,the above 4 parameters in experimental group were all significantly different with those in control group(all P＜0.05).LASr,LASct and LASI were different among different time points,while LAScd before injection was higher than that 2 and 4 weeks after injection in experimental group(all P＜0.05).The pathological findings supported ultrasonic changes.Conclusion In early stage of ADM induced left ventricular myocardial injury in rabbits,changes of left atrial strain and LASI could be seen,which were more significant than those of LVGLS,RVCLS and LVEF,etc.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

This study aims to investigate the protective effect and potential mechanism of Jingfang Granules(JF) on the mouse model of chronic fatigue syndrome(CFS). Mice were randomized into normal, model, and low-, medium-, and high-dose(0.9, 1.8, and 3.6 g·kg~(-1)·d~(-1), respectively) JF groups according to the body weight. In addition to the normal group, other groups of mice received exhaustive swimming training and tail suspension training every day for the modeling of CFS. The mice in each administration group were administrated with JF at the corresponding dose by gavage, and those in the other groups were administrated with an equal amount of purified water. The exhaustive swimming and tail suspension tests were conducted in each group. The UV-glutamate dehydrogenase method was used to determine the serum level of urea nitrogen(UREA), and the lactate dehydrogenase(LDH) assay kit was used to determine the LDH level. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum, muscle tissue, and brain tissue of mice in each group. Western blot was employed to determine the expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappa B(NF-κB) and their phosphorylated proteins in the muscle tissue of mice. The 16S rDNA sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) were adopted to detect the changes of intestinal flora and intestinal metabolites in mice. Compared with the model group, JF significantly prolonged the swimming exhaustion time and shortened the tail suspension time of the model mice, lowered the levels of LDH and UREA in the serum as well as the levels of IL-6 and TNF-α in the serum, muscle tissue, and brain tissue of CFS mice. In addition, JF down-regulated the expression of TLR4, MyD88, and p-NF-κB/NF-κB in the muscle tissue of CFS mice compared with the model group. The results of 16S rDNA sequencing demonstrated that JF ameliorated the intestinal flora disorder of CFS mice. The results of UPLC-MS/MS revealed that JF significantly affected the histidine metabolism pathway in the intestinal tract of CFS mice. Spearman analysis displayed that histamine, a metabolite involved in histidine metabolism, was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. The metabolite imidazole-4-acetaldehyde was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. In conclusion, JF can increase the swimming exhaustion time, reduce the immobility time of tail suspension, lower serum LDH and UREA levels, and alleviate inflammation response. It may exert the therapeutic effect by improving intestinal flora homeostasis and inhibiting histidine metabolism by down-regulating the expression of proteins in the TLR4/MyD88/NF-κB signaling pathway, thereby relieving the symptoms of CFS in mice.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Metabolomics ; Fatigue Syndrome, Chronic/genetics* ; NF-kappa B/genetics* ; Humans ; Interleukin-6/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Disease Models, Animal

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.
Rats ; Male ; Animals ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Nerve Growth Factor/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism* ; Serotonin/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Antidepressive Agents/pharmacology* ; Hippocampus/metabolism* ; Superoxide Dismutase/metabolism* ; Sugars/pharmacology* ; Depression/genetics* ; Stress, Psychological/metabolism*

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 μmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 μmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.
Animals ; Reactive Oxygen Species/metabolism* ; Antioxidants/pharmacology* ; Oxidative Stress ; NF-E2-Related Factor 2/metabolism* ; Caspase 3/metabolism* ; Parkinson Disease/genetics* ; bcl-2-Associated X Protein/metabolism* ; Neuroprotective Agents/pharmacology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Drosophila/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Superoxide Dismutase/metabolism* ; Adenosine Triphosphate/pharmacology*

Objective:To explore the value of transapical catheter of mitral valve repair (MVR) with Memoclip device in the management of moderate to severe and severe mitral regurgitation (MR) guided by transesophageal echocardiography (TEE).Methods:Fifteen patients with moderate to severe and severe MR in Hefei High-tech Cardiovascular Hospital from December 2021 to October 2022 were prospectively selected. Mitral valve morphology and length, regurgitation severity, left ventricular ejection fraction and pulmonary venous Doppler spectra were carefully evaluated before MVR by TEE.Intraprocedural TEE was performed to guide the MVR including transseptal catheterization, alignment of the clip delivery system, assessment of leaflet capture, clip deployment, post-clip deployment assessment, and withdrawal of the clip delivery system. The position and coaptation length of the clips, the mitral orifice morphology, residual mitral valve regurgitation and pressure gradient were evaluated after MVR.Meanwhile, the complications were monitored throughout the procedure.Results:Among the 15 patients, 12 were implanted with 1 clip and 3 were implanted with 2 clips, respectively. No complications occurred. There were 13 patients with mild regurgitation and 2 showed to moderate mitral regurgitation 1 month later after MVR, and 13 remained mild and 2 maintained moderate regurgitation 3 months later. Significant differences were found in maximal MR area (MRA-max), maximal and mean mitral valve pressure gradient (MVPG-max, MVPG-mean) and mitral valve area (MVA) among the 5 observation time points (all P<0.05). MRA-max, MVA and MVPG-mean were significantly decreased immediately and 3 months after the procedure ( P<0.001). No significant stenosis was found in mitral valve after MVR. Conclusions:MVR with Memoclip is safe, effective, easy to operate in treating patients with moderate to severe and severe MR. TEE plays a key role in perioperative MVR with Memoclip through apical catheterization.