BackgroundPatients with depressive episode and schizophrenia have a high risk of suicide. The sleep electroencephalogram power spectral density characteristics of patients with depressive episode accompanied by suicidal behavior and those with schizophrenia may be different， but there is currently a lack of direct comparative studies on these two groups of patients. ObjectiveTo compare the sleep electroencephalogram power spectral density between depressive episode and schizophrenic patients with suicidal behavior， in order to provide references for exploring predictive indicators of suicidal behavior. MethodsFrom June 2018 to December 2020， 20 patients with depressive episode and 20 patients with schizophrenia who had committed suicide within the past month and were treated at the outpatient department of Shenzhen Kangning Hospital were selected. All of them met the diagnostic criteria for depressive episode or schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）. Using a random sampling method， 20 volunteers with matching gender and age to the patient groups were selected from the Cuiping community in Shenzhen as the control group. The subjective sleep of the patients was evaluated using the Insomnia Severity Index （ISI）， the Dysfunctional Belief and Attitude about Sleep （DBAS）， the Disturbing Dreams and Nightmare Severity Index （DDNSI）， and the Epworth Somnolence Scale （ESS）. The objective sleep of the patients was assessed using polysomnography. The sleep electroencephalogram was filtered and the power spectral density of the brain wave was analyzed and processed for all the subjects. The subjective and objective sleep conditions of the two patient groups were compared， and the sleep electroencephalogram power spectral density of the patient groups and the control group were also compared. ResultsA comparison of subjective and objective sleep conditions between patients with depressive episode accompanied by suicidal behavior and patients with schizophrenia accompanied by suicidal behavior showed no statistically significant differences （P>0.05）. Comparisons of sleep electroencephalogram power spectral density in the W stage （average power of α wave， total power of δ wave， average power of δ wave， average power of θ wave）， N1 stage （average power of β wave， total power of α wave， total power of δ wave）， N2 stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave）， N3 stage （average power of α wave， average power of δ wave）， and R stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave） between patients with depressive episode accompanied by suicidal behavior， patients with schizophrenia accompanied by suicidal behavior， and the control group showed statistically significant differences （P<0.05 or 0.01）. The total power of δ wave in the W stage and the average power of β wave and δ wave in the N1 stage were higher in two patient groups were higher than those of the control group. The total power of α wave and the average power of α wave in the N2 stage were lower than those of the control group， while the average power of δ wave was higher than that of the control group. The average power of α wave in the N3 stage of both patient groups were lower than that of the control group， while the average power of δ wave was higher than that of the control group. The total power and average power of α wave in the R stage were lower than those of the control group， while the total power and average power of δ wave were higher than those of the control group. All the differences were statistically significant. Patients with depressive episode accompanied by suicidal behavior had higher average powers of α wave， δ wave， and θ wave in the W stage compared with the control group， while the total power of α wave in the N1 stage was lower in the former group. All these differences were statistically significant （P<0.05）. ConclusionThe depressive episode patients accompanied by suicidal behavior have highly overlapping sleep electroencephalogram abnormal patterns with those of schizophrenia patients， mainly manifested as a general decrease in α wave power （N2， N3， R stage） and a general increase in δ wave power （W， N1， N2， N3， R stage） as well as β wave power in N1 stage. At the same time， patients with depressive episode accompanied by suicidal behavior also show specific changes， including an increase in the average power of α and θ waves during the wakefulness period （W stage）， and a decrease in the total power of α wave in N1 stage. ［Funded by Guangdong Province High-level Clinical Key Specialty （with supporting funds from Shenzhen City） （number， SZGSP013）； Shenzhen Key Medical Discipline （number， SZXK041）； Shenzhen Clinical Medicine Research Center Project （number， 20210617155253001）］

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective To explore the implementation effect of PDCA(plan-do-check-action)style training of severe ultrasound and hemodynamics in standardized training(residential training)for residents majoring in internal medicine on improving their clinical decision-making ability.Methods A retrospective research method was conducted,60 residents in Xinyang Central Hospital from July 2017 to July 2023 were selected as the research objects,and patients were randomly divided into experimental group and control group,with 30 residents in each group.After the routine entrance education,the experimental group applied the PDCA mode training of severe ultrasound and hemodynamics.The control group was trained with the training objectives and requirements of the department of critical care medicine in the contents and standards of standardized training for internal medicine residents for 2 months.At the end of the training period,the residents of the two groups were assessed and investigated by questionnaire,and the differences of theoretical knowledge assessment,clinical practice skills assessment,case assessment scores and satisfaction between the two groups were compared.Results The results of theoretical knowledge examination,diagnosis and differential diagnosis,and clinical decision-making in the experimental group were significantly higher than those in the control group(theoretical knowledge examination score:90.5±2.7 vs.85.7±3.8,diagnosis and differential diagnosis score:92.0±2.4 vs.87.9±3.7,clinical decision-making score:90.3±3.1 vs.85.5±3.9,all P<0.05),satisfaction with teaching methods,stimulating learning interest,firmly mastering knowledge,enhancing problem-solving ability,improving learning enthusiasm,improving clinical thinking ability and enhancing team consciousness was also significantly higher than that of the control group[teaching methods:80.0%(24/30)vs.46.7%(14/30),stimulate learning interest:83.3%(25/30)vs.56.7%(17/30),firmly mastering knowledge:80.0%(24/30)vs.40.0%(12/30),enhance problem-solving ability:70.0%(21/30)vs.43.3%(13/30),improving learning enthusiasm:83.3%(25/30)vs.50.0%(15/30),improving clinical thinking ability:60.0%(18/30)vs.40.0%(12/30),enhancing team consciousness:73.3%(22/30)vs.46.7%(14/30),all P<0.05].Conclusion The application of PDCA-style training of severe ultrasound and hemodynamics can help internal medicine residents master the basic theory and skills of severe diseases faster and better in the rotation of critical medicine departments,which is more conducive to improving the clinical decision-making ability of internal medicine residents.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.

Objective It conducted a rapid health technology assessment to evaluate the comparative safety,efficacy and economy of tumor treating fields(TTFields)combined with temozolomide treatment versus temozolomide(TMZ)alone for patients with glioblastoma(GBM).Methods It provided an extensive electronic search of databases,including PubMed,Embase,Cochrane Library,CNKI,and WanFang Data,to collect clinical evidence and health economic evaluations related to the,safety,efficacy,and economy of TTFields for Glioblastoma patients.The search covered literature from inception to July,2023,and assessed the risk of bias in the included studies.Descriptive analyses and data summaries were performed.Results A total of 19 references were included,comprising 5 randomized controlled trials,3 retrospective studies,8 systematic reviews or meta-analyses,and 3 cost-effectiveness analysis(CEA)studies.The quality of the literature evidence was heterogeneous.Recent meta-analyses mostly support the conclusion that TTFields combined with TMZ treatment provides a survival benefit compared to standard TMZ alone.However,the cost-effectiveness analysis literature from 2 countries showed different results,likely due to differences in socioeconomic levels,health systems,and heterogeneity in sources,model selection,and parameter selection.The majority of evidence supports the benefits of TTFields combined with TMZ for the treatment of GBM patients,but the results of CEAs tend to favor the view that this therapy is not cost-effective.Conclusion Current evidence indicates that TTFields combined with TMZ treatment have better safety and efficacy.However,there is still no consensus on whether it is cost-effective.