Objective To observe the effects of wheat grain moxibustion on the hippocampal ERK/CREB-BDNF/TrkB signaling pathway and neurotransmitters in rats with perimenopausal depressive disorder(PDD);To explore its mechanism in treating PDD.Methods Totally 24 female SD rats were randomly divided into sham-operation group,model group,Western medicine group and wheat grain moxibustion group,with 6 rats in each group.The PDD rat model was established by bilateral ovariectomy and chronic unpredictable mild stress.The wheat grain moxibustion group received moxibustion at the"Zhongwan","Xiawan","Qihai","Guanyuan"acupoints,with a conical moxa cone for intervention,6 cones per acupoint;the Western medicine group was given fluoxetine hydrochloride solution 1.8 mg/kg by gavage,once a day,for consecutive 21 d.Before and after modeling and after intervention,the body mass,sucrose water preference rate and immobility time in the forced swimming test of the rats were recorded;Transmission electron microscopy was used to observe the synaptic structure in hippocampal tissue;ELISA was used to detect the expressions of 5-HT,GABA and Glu in hippocampal tissue;Western blot was used to detect the expressions of ERK,p-ERK,CREB,p-CREB,BDNF and TrkB proteins in hippocampal tissue.Results Compared with the sham-operation group,the body mass and sucrose water preference rate of the model group decreased,and the immobility time in the forced swimming test was prolonged(P<0.01);the number of synaptic vesicles in hippocampus decreased,the thickness of the postsynaptic density decreased,the aggregation of transduction-related proteins decreased,the synaptic cleft increased;the contents of 5-HT and GABA in hippocampal tissue decreased,the content of Glu increased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins decreased(P<0.01).Compared with the model group,the body mass and sucrose water preference rate of the rats in Western medicine group and wheat grain moxibustion group increased,and the immobility time in the forced swimming test was shortened(P<0.01);the area of the postsynaptic density in the hippocampus increased,the synaptic cleft reduced,the contents of 5-HT and GABA in hippocampal tissue increased,the content of Glu decreased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins increased(P<0.01).Conclusion Wheat grain moxibustion can effectively alleviate depressive-like behavior in PDD rats,and its mechanism may be related to regulating neurotransmitter expressions and mediating the ERK/CREB-BDNF/TrkB signaling pathway,thereby regulating hippocampal neuroplasticity.

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Hegu" (LI4) and "Taichong" (LR3) on DNA methylation of the solute carrier family 6 member 4 (SLC6A4) gene promoter region in the hippocampus of depressed rats, and to explore the potential antidepressant mechanism of EA. METHODS: Thirty male Sprague-Dawley rats were randomly divided into a blank group, a model group, a medication group, a 5-Azacytidine (5-AZA) group, and an EA group, 6 rats in each group. Depression models were established in the model group, the medication group, the 5-AZA group, and the EA group using chronic unpredictable mild stress (CUMS) combined with solitary housing. The medication group was treated with intragastric administration of fluoxetine hydrochloride capsules; the 5-AZA group was treated with intraperitoneal injection of 5-AZA; the EA group was treated with EA at bilateral "Hegu" (LI4) and "Taichong" (LR3), with disperse-dense wave, frequency of 2 Hz/100 Hz, and intensity of 1-1.2 mA, 20 min each session. All the treatment was given in three groups once daily for 21 consecutive days. Behavioral changes were evaluated by sucrose preference test, open field test, and novelty-suppressed feeding test. Serum levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured by ELISA. The expression of SLC6A4 and 5-HT1AR protein and mRNA in hippocampus was detected by Western blot and real-time quantitative PCR, respectively. DNA methylation status of the SLC6A4 promoter region in hippocampal tissue was analyzed by bisulfite sequencing PCR (BSP). RESULTS: Compared with the blank group, the model group showed decreased sucrose preference, reduced total locomotor distance, and prolonged latency to feeding (P<0.05), decreased serum 5-HT, DA, and NE levels (P<0.05), downregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and increased CpG site methylation rate of the SLC6A4 promoter region (P<0.05). Compared with the model group, the medication group, the 5-AZA group, and the EA group exhibited increased sucrose preference, increased total locomotor distance, shortened latency to feeding (P<0.05), elevated serum 5-HT, DA, and NE levels (P<0.05), upregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and reduced CpG site methylation rate of the SLC6A4 promoter (P<0.05). Compared with the medication group and the 5-AZA group, the EA group showed higher sucrose preference, greater total locomotor distance, shorter latency to feeding (P<0.05), and increased serum DA and NE levels (P<0.05). CONCLUSION EA could improve depressive behaviors in depressed rat models. The underlying mechanism may involve inhibition of SLC6A4 hypermethylation in the hippocampus on the serotonergic system, upregulation of SLC6A4 and 5-HT1AR protein and mRNA expression, and elevation of monoamine neurotransmitters such as 5-HT.
Animals ; Electroacupuncture ; Male ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; DNA Methylation ; Depression/metabolism* ; Promoter Regions, Genetic ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Humans

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To observe the effects of wheat grain moxibustion on the hippocampal ERK/CREB-BDNF/TrkB signaling pathway and neurotransmitters in rats with perimenopausal depressive disorder(PDD);To explore its mechanism in treating PDD.Methods Totally 24 female SD rats were randomly divided into sham-operation group,model group,Western medicine group and wheat grain moxibustion group,with 6 rats in each group.The PDD rat model was established by bilateral ovariectomy and chronic unpredictable mild stress.The wheat grain moxibustion group received moxibustion at the"Zhongwan","Xiawan","Qihai","Guanyuan"acupoints,with a conical moxa cone for intervention,6 cones per acupoint;the Western medicine group was given fluoxetine hydrochloride solution 1.8 mg/kg by gavage,once a day,for consecutive 21 d.Before and after modeling and after intervention,the body mass,sucrose water preference rate and immobility time in the forced swimming test of the rats were recorded;Transmission electron microscopy was used to observe the synaptic structure in hippocampal tissue;ELISA was used to detect the expressions of 5-HT,GABA and Glu in hippocampal tissue;Western blot was used to detect the expressions of ERK,p-ERK,CREB,p-CREB,BDNF and TrkB proteins in hippocampal tissue.Results Compared with the sham-operation group,the body mass and sucrose water preference rate of the model group decreased,and the immobility time in the forced swimming test was prolonged(P<0.01);the number of synaptic vesicles in hippocampus decreased,the thickness of the postsynaptic density decreased,the aggregation of transduction-related proteins decreased,the synaptic cleft increased;the contents of 5-HT and GABA in hippocampal tissue decreased,the content of Glu increased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins decreased(P<0.01).Compared with the model group,the body mass and sucrose water preference rate of the rats in Western medicine group and wheat grain moxibustion group increased,and the immobility time in the forced swimming test was shortened(P<0.01);the area of the postsynaptic density in the hippocampus increased,the synaptic cleft reduced,the contents of 5-HT and GABA in hippocampal tissue increased,the content of Glu decreased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins increased(P<0.01).Conclusion Wheat grain moxibustion can effectively alleviate depressive-like behavior in PDD rats,and its mechanism may be related to regulating neurotransmitter expressions and mediating the ERK/CREB-BDNF/TrkB signaling pathway,thereby regulating hippocampal neuroplasticity.

N6-methyladenosine(m6A)modification is one of the most abundant epitranscriptomic modifications in eukaryotic mRNA,with dynamic and reversible properties.This modification process is coordinated by methyltransferases,demethylases,and related m6A binding proteins,which in turn affect mRNA metabolism and function.Increasing evi-dence has indicated that the m6A RNA modification plays an important role in the occurrence and development of athero-sclerosis(As)and other related diseases.This paper provide a comprehensive review of the relationship between m6A RNA modification and As.The entire manuscript summarizes the m6A RNA modification mechanism and its roles in As-related cells including endothelial cells,macrophages,and smooth muscle cells,and discusses the association of m6A RNA modification with risk factors of As such as high-fat diet,ischemia/hypoxia,oscillatory stress,and hypertension.Finally,this review summarizes researches on drug intervention targeting m6A RNA methylation to mitigate As.These studies pro-vide important references for exploring new targets for early diagnosis and treatment of As.

Objective To observe the effects of wheat grain moxibustion for"Huantiao"on sciatic nerve function,pathological morphology of sciatic nerve stem and expressions of TLR4/MyD88/NF-κB signaling pathway expression in spinal cord tissue of rats with sciatic nerve injury(SNI);To explore the possible mechanism of wheat grain moxibustion for the treatment of SNI.Methods Totally 24 SD male rats were randomly divided into blank group,sham-operation group,model group and wheat grain moxibustion group,with 6 rats in each group.The model group and the wheat grain moxibustion group used a rat model with sciatic nerve clamping injury.From the 7th day after modeling,the rats were treated with moxibustion on the affected side of"Huantiao"for 6 strokes each time,once a day,for consecutive 10 days.The sciatic nerve function index(SFI)of rats on the 7th day after modeling and after intervention were observed,mechanical withdraw threshold(MWT)in rats were measured using a fiber optic pain gauge,ELISA was used to detect NO and iNOS content in spinal cord tissue,HE staining was used to observe the morphology of sciatic nerve stem,the expression of TLR4,NF-κBp65,p-NF-κBp65,MyD88,IκBα and p-IκBα in spinal cord tissue were detected by Western blot.Results Compared with the sham-operation group,the SFI and MWT of the rats in the model group significantly decreased(P<0.01),the arrangement of nerve fibers in sciatic nerve stem was disordered,with a significant increase in the number of Schwann cells and a large number of vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα protein in spinal cord tissue significantly increased(P<0.01).Compared with the model group,the SFI and MWT of the rats in the wheat grain moxibustion group increased significantly(P<0.01),the damage of sciatic nerve stem was reduced,with orderly cell arrangement,a decrease in the number of Schwann cells,and a decrease in axonal demyelination and cellular vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα in spinal cord tissue significantly decreased(P<0.05).Conclusion Wheat grain moxibustion for"Huantiao"can down-regulate TLR4,p-NF-κBp65,MyD88 and p-IκBα protein expressions in spinal cord tissue of SNI rats,reduce the secretion of NO and iNOS,thereby relieve pain and damaged nerve tissue inflammation response.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To investigate the relationship between abdominal visceral adipose tissue (VAT) and cardiometabolic risk (CMR) through quantitative computed tomography (QCT).Methods:The present study included 76226 participants. Abdominal fat areas were measured using the QCT Pro Model 4 system. Cardiometabolic indices were collected, including systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterols CMR score was the sum of abnormal blood pressure, fasting glucose, triglyceride, and high-density lipoprotein cholesterol. Restricted cubic spline and ordered logistic regression models were applied.Results:The mean age was 50±13 years and the percentage of men was 58.8%. The level of VAT area was higher in men than in women (191.7±77.1 cm 2 vs 116.4±56.2 cm 2, P<0.0001 for all). After adjustment for age, the cardiometabolic indices except high-density lipoprotein cholesterol increased with increasing VAT area. When VAT area was 300 cm 2, age-adjusted odds ratios and 95% confidence intervals of a CMR score ≥ 1 were 14.61 (13.31, 16.04) for men and 5.46 (4.06, 7.36) for women, and the age-adjusted probability of a CMR score ≥ 3 was 31.7% for men and 31.3% for women. Conclusions:QCT-derived VAT is closely related to CMR. The findings suggest that measurement of visceral fat is recommended for the management of abdominal obesity in subjects who agree to undergo lung cancer screening via low-dose CT without additional radiation exposure.