Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Isolated unilateral oculomotor palsy caused by pure midbrain infarction: a case report.

Purpose: Multiple etiologies may cause oculomotor nerve palsies. Identification of different etiologies is very important for subsequent treatment. Midbrain infarction is a rare cause of oculomotor nerve palsy. Materials and methods: We herein present a case of isolated unilateral oculomotor paresis caused by pure midbrain infarction. Results: Her pupillary sphincter and inferior rectus muscles were selectively spared. The symptoms were completely relieved after two months of antiplatelet therapy. We proposed that fibers from Edinger-Westphal nucleus and inferior rectus nucleus do not course through the paramedian area of the midbrain. Conclusions: Our report adds to the understanding of fascicles arrangement in the midbrain.

Auricular Vagus Nerve Stimulation Ameliorates Functional Dyspepsia with Depressive-Like Behavior and Inhibits the Hypothalamus-Pituitary-Adrenal Axis in a Rat Model.

BACKGROUND: The hypothalamus-pituitary-adrenal axis is the most important endocrine system to control irritability response. Functional dyspepsia (FD) is closely related to irritability. This study aimed to preliminarily explore the corticotropin-releasing factor (CRF) mechanism of auricular vagus nerve stimulation (aVNS) for FD model rats. METHODS: Sprague-Dawley adult male rats were randomly divided into normal group, model group, aVNS group, and sham-aVNS group. Except for the normal rats, all other rats were induced into the FD model through tail-clamping stimulation for 3 weeks. Once the rat model was developed successfully, rats in the aVNS group and sham-aVNS group were intervened with aVNS or sham-aVNS for 2 weeks. No intervention was given to rats in the normal and model groups. The effect of aVNS was assessed. The expressions of hippocampal corticotropin-releasing hormone receptor 1 (CRHR1), hypothalamus CRF, adrenocorticotropic hormone (ACTH), and corticosterone in serum were assessed. RESULTS: 1. Compared with normal rats, model-developing rats showed FD-like behavior. 2. Compared with model rats, rats in the aVNS group showed an improved general condition score and gastric motility, and increased horizontal and vertical motion scores. 3. The release of corticosterone, ACTH in serum, and CRF in the hypothalamus all increased in model rats but decreased with aVNS instead of sham-aVNS. 4. The expression of hippocampus CRHR1 was lower in model rats but higher in the aVNS group. CONCLUSION: aVNS ameliorates gastric motility and improves the mental state in the FD-like rat, probably via inhibiting the CRF pathway.

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants. METHODS: Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed. RESULTS: All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1ß (IL-1ß). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1ß but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity. CONCLUSIONS: The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.

Assessor- and participant-blinded, randomized controlled trial of dense cranial electroacupuncture stimulation plus body acupuncture for neuropsychiatric sequelae of stroke.

AIM: Acupuncture has benefits in the rehabilitation of neuropsychiatric sequelae of stroke. This study was aimed to evaluate the effectiveness of dense cranial electroacupuncture stimulation plus body acupuncture (DCEAS+BA) in treating poststroke depression (PSD), functional disability, and cognitive deterioration. METHODS: In this assessor- and participant-blinded, randomized controlled trial, 91 stroke patients who initially had PSD were randomly assigned to either DCEAS+BA (n = 45) or minimum acupuncture stimulation as controls (n = 46) for three sessions per week over 8 consecutive weeks. The primary outcome was baseline-to-end-point change in score of the 17-item Hamilton Depression Rating Scale. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Barthel Index for functional disability, and the Montreal Cognitive Assessment for cognitive function. RESULTS: DCEAS+BA-treated patients showed strikingly greater end-point reduction than MAS-treated patients in scores of the three symptom domains. The clinical response rate, defined as an at least 50% baseline-to-end-point reduction in 17-item Hamilton Depression Rating Scale score, was markedly higher in the DCEAS+BA-treated group than that of controls (40.0% vs 17.4%, P = 0.031). Incidence of adverse events was not different in the two groups. Subgroup analysis revealed that DCEAS+BA with electrical stimulation on forehead acupoints was more apparent in reducing Barthel-Index-measured disability than that without electrical stimulation. CONCLUSION: DCEAS+BA, particularly with electrical stimulation on forehead acupoints, reduces PSD, functional disability, and cognitive deterioration of stroke patients. It can serve as an effective rehabilitation therapy for neuropsychiatric sequelae of stroke.

[Molecular mechanisms of meiotic recombination suppression in plants].

Meiotic recombination not only ensures the stability of chromosome numbers during the sexual reproduction in eukaryotes, but also shuffles the maternal and paternal genetic materials to generate genetic diversity in the gametes. Therefore, meiotic recombination is an important pathway for genetic diversity, which has been considered as a major driving force for species evolution and biodiversity in nature. In most eukaryotes, meiotic recombination is strictly limited, despite the large variation of physical genome size and chromosome numbers among species, but the mechanisms suppressing meiotic recombination remain elusive. Recently, several suppressors have been identified through the forward genetics screen, and revealed the functions and regulation pathways of these suppressors. In this review, we summarize the breakthrough discovery of meiotic recombination suppressors in plants based on research in Arabidopsis, with particular focus on the gene function and its regulation network to elucidate the molecular mechanisms of meiotic recombination suppression in plants.

Effect of serum uric acid on cognition in patients with idiopathic REM sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) likely represents the prodromal stage of synucleinopathy. The present study investigated how levels of serum uric acid (UA) affect cognition and motor function in patients with iRBD. A total of 42 patients with iRBD and 45 healthy controls were included. All participants were given cognitive tests and motor assessments. Serum UA concentrations were measured. The patients were further divided into two groups (high or low UA) according to serum UA level. The level of serum UA was similar between the patients with iRBD and the healthy controls, whereas the patients showed impaired executive, memory, and visuospatial functions. The patients with low UA levels had longer durations of RBD. Lower scores involving attention, executive function, and language domain were also found in the patients with low UA, whereas the scores of the patients with high UA were similar to those of the healthy controls. Regarding memory domain, the low UA group had worse scores than the healthy controls, whereas the scores of high UA group fell between those of the low UA group and the healthy controls. Motor function was not affected in any of the groups. UA affects cognitive function but not motor function in patients with iRBD, which could contribute to its antioxidant and neuroprotective roles.

The role of the Montreal Cognitive Assessment (MoCA) and its memory tasks for detecting mild cognitive impairment.

To investigate the role of the Montreal Cognitive Assessment (MoCA) (Beijing version) and its memory tasks on detecting different mild cognitive impairment (MCI) subtypes including amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in memory clinics. A total of 121 patients with MCI and 53 healthy controls were included. Fifty-six aMCI-multiple domains (amMCI), 32 aMCI-single domain (asMCI), and 33 naMCI patients were diagnosed according to extensive cognitive tests. All participants were administered by the Mini Mental State Examination (MMSE) and the MoCA. Patients with amMCI performed worse than patients with asMCI, naMCI, and healthy controls on the MMSE and the MoCA (p < 0.001). The area under the curve (AUC) value for the MoCA when comparing the amMCI and control groups was 0.884 (p < 0.001), which was superior to that of the MMSE. The AUC value decreased to 0.687 when applied to the naMCI and control groups (p = 0.007), which was still higher than that of the Rey Auditory Verbal Learning Test (RAVLT) or the Rey-Osterrieth complex figure (ROCF). Delayed free recall or category prompted recall in the MoCA had roles in differentiating asMCI and controls groups with AUC value of 0.717 (p = 0.002) and 0.691 (p = 0.005), respectively. The MoCA is a good screening tool for detecting different types of MCI and is suitable for patients in outpatient clinics.

Transcranial sonography in idiopathic REM sleep behavior disorder and multiple system atrophy.

AIM: We investigated preclinical abnormalities as revealed by transcranial sonography (TCS) in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) compared with those revealed in patients with multiple system atrophy (MSA) or Parkinson's disease (PD) and in normal controls. METHODS: Twenty-two patients with iRBD, 21 patients with MSA, 22 patients with PD, and 21 normal controls were included in this study. All participants underwent one night of video-polysomnography monitoring, and the sleep parameters were analyzed using Polysmith software and by visual analysis. TCS was performed following a standardized procedure. The echogenicity of the substantia nigra and basal ganglia were evaluated. RESULTS: A greater proportion of PD patients were found to have substantia nigra hyperechogenicity (86.4%) when compared to iRBD patients (31.8%), MSA patients (23.8%), and normal controls (4.8%) (P < 0.001). Fourteen MSA patients (66.7%) and 11 iRBD patients (50.0%) had hyperechogenicity in the basal ganglia, whereas hyperechogenicity in the basal ganglia was less frequent in PD patients (18.2%) and normal controls (9.5%) (P < 0.001). Poor sleep efficiency, less stage II sleep time, and more periodic leg movements were found in MSA and PD patients, whereas iRBD patients had almost normal sleep. CONCLUSION: Some iRBD patients had basal ganglia hyperechogenicity that was similar to that observed in MSA, which may represent another possible convert direction. The present study further confirmed iRBD as a prodromal stage of synucleinopathy. TCS could detect subclinical changes and thus might provide useful markers for identifying individuals at increased risk for developing a synucleinopathy.

[Effect of Needle Embedded in Neiguan (PC6) on Changes of ECG in Chronic Myocardial Ischemia Model Mini-pigs].

Objective To observe the effect of needle embedded in Neiguan (PC6) on electro- cardiogram (ECG) changes in model mini-pigs with chronic myocardial ischemia. Methods The protein shrink narrow ring (Ameroid Ring) was placed in the proximal part of the left coronary anterior descend- ing branch of 12 Chinese mini-pigs to prepare animal model. One died during the modeling. Chronic myo- cardial ischemia mini-pig models were established after 4 weeks. Successfully modeled 11 mini-pigs were divided into the test group (n =6) and the control group (n =5). Needle were embedded in Neiguan (PC6) of the test group and Zusanli (ST36) of the control group at week 4 after modeling. Electroacupuncture (EA) at corresponding acupoint twice (once before embedding and at week 2 after embedding) , 20 min each time. Changes of Q wave of ECG, heart rate, and ST-T interval were observed in the two groups be- fore and after modeling, before and after EA. Results Compared with before modeling in the same group, the absolute value of Q wave both increased in the two groups after modeling (P <0. 05, P <0. 01J. No statistical difference existed in heart rate in the two groups between before and after modeling (P> 0. 05). Compared with before needling in the same group, ST-T interval was prolonged in the test group (P <0. 05). Compared with the control group at the same time point, the absolute value of Q wave was re- duced before EA, ST-T interval was prolonged after EA in the test group (P <0. 05). No statistical differ- ence existed in heart rate between the control group and the test group before EA (P >0. 05). Conclusion Needle embedded in Neiguan (PC6) could arrive at therapeutic effect of myocardial ischemia possibly through improving myocardial blood supply.

[Effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model].

In order to investigate the effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model and the possible mechamism, the experimental mice were randomly divided into 4 groups: control, Shouwu Shudi Yin, MPTP and the treatment (MPTP+Shouwu Shudi Yin) groups. The number of tyrosine hydroxylase (TH) positive cells in the substantia nigra was measured by immunohistochemistry, and mRNA expression of TH and glutathione peroxidase (GPX) were detected by PCR. The results showed that the number of TH positive cells and mRNA expression of TH were significantly reduced in MPTP group compared with the control (P<0.05), and pretreated with Shouwu Shudi Yin didn't show protective effect. Compared to MPTP group, the mRNA expression of four subtypes of GPX were increased in various degrees in the treatment group pretreated with Shouwu Shudi Yin, although the difference was not statistically significant. These indicated that the preventive medication of Shouwu Shudi Yin don't have protective effect on the mice with Parkinson' s disease induced by MPTP, but it may enhance the antioxidant capacity through increasing the expression of GPX.

The Beneficial Effects of Electro-acupuncture at PC6 (Neiguan-point) of Gene and Protein Expressions of Classical Inward-rectifier Potassium Channels in Myocardial Ischemic Rats.

This study is aim to investigate the effect of electro-acupuncture at PC6 (Neiguan-point) on the gene and protein expressions of classical inward-rectifier potassium channels (Kir) in myocardial ischemia (MI) rats induced by isoproterenol (ISO). With ten for each one, 50 rats were divided into 5 groups which were control group, MI group, PC6 group, LU7 (Lieque-point) group and non-acupoint group. The control group was injected normal saline solution (85 mg/kg), the other groups were injected ISO (85 mg/kg). All the rats were injected once daily for two days and recorded electrocardiograms (ECGs) after every injection. Electro-acupuncture (EA) was operated at PC6, LU7 and non-acupoint respectively in the rats of PC6 group, LU7 group and non-acupoint group after twice injections. EA was performed to these three groups with disperse-dense wave (4-20 Hz), pulse amplitude of 14V, 20 mins a day remaining 7 days. The gene and protein expressions of Kir2.1, Kir2.2 and Kir2.3 were analyzed by Western Immunoblotting Technology (Western Blot) and Real-time Fluorescence Quantitative Polymerase Chain Reaction (RT-PCR). But it is regrettable that we did not detect meaningful gene and protein expressions Kir2.3, and the expressions of Kir2.1 and Kir2.2 in MI induced groups were lower [The gene and protein decreased 39.4 ± 27.3% and 38.7 ± 17.1% respectively.] than control group (P < 0.05). Compared with MI group, the results of PC6 group and LU7 group increased [PC6 group: the gene and protein increased 42.9 25.0% and 42.2 ± 10.0% respectively. LU7 group: the gene and protein increased 23.8 ± 50.1% and 21.1 ± 32.5% respectively.] obviously (P < 0.05) after EA, furthermore the expressions of PC6 group were higher [The gene and protein increased 15.4 ± 16.7% and 17.3 ± 60% respectively.] than LU7 group (P < 0.05). The results show that PC6 has a better positive effect than LU7 on MI rats, and the mechanism is probably that EA at PC6 can significantly increase the gene and protein expressions of Kir2.1 and Kir2.2.

Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling.

BACKGROUND: Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson's disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s). METHODS: BV2 and primary microglial cells were pretreated with paroxetine and stimulated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed in BV2 cells. RESULTS: Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α and IL-1ß. Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1ß were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activation of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity. CONCLUSIONS: Paroxetine inhibits LPS-stimulated microglia activation through collective regulation of JNK1/2 and ERK1/2 signaling. Our results indicate a potential role of paroxetine in neuroprotection via its anti-neuroinflammatory effect besides targeting for depression.

Possible mechanisms of auricular acupoint stimulation in the treatment of migraine by activating auricular vagus nerve. / 从耳迷走神经探讨耳穴治疗偏头痛的可能机制.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Hypertension - the difficult decisions.

BACKGROUND: Although management of hypertension is a daily activity of primary care practitioners, it remains one of the most demanding areas of medicine. Reasons for this include the imprecision of blood pressure measurement, the complexity of assessing cardiovascular risk, and the need to use multiple agents to control blood pressure. OBJECTIVE: This article discusses clinical scenarios that force clinicians to make decisions about blood pressure measurement techniques and methods of treatment. DISCUSSION: We consider ambulatory compared to office based blood pressure measurement, the types of clinical scenarios in which ambulatory blood pressure monitoring is likely to be beneficial, what to consider when there is nocturnal elevated blood pressure, and the assessment and management of resistant hypertension.

Acupoint stimulation for long COVID: A promising intervention:.

"Long COVID" is a sustained symptom following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to recent statistics, at least 65 million people have long COVID, which poses a long-term threat to human health. The pathogenic mechanisms of coronavirus disease 2019 (COVID-19) are complex and affect multiple organs and systems. Common symptoms include palpitations, breathing difficulties, attention and memory deficits, fatigue, anxiety, and depression. It is difficult to achieve satisfactory treatment effect with a single intervention. Currently, treatment strategies for long COVID are still in the exploratory stage, and there is an urgent need to find appropriate and effective methods for long COVID treatment. Traditional Chinese medicine is effective in treating the various phases of COVID-19. Previous studies have shown that acupoint stimulation therapy is effective in improving palpitations, dyspnea, cognitive impairment, anxiety, depression, and other symptoms in patients. According to previous studies, acupoint stimulation may improve various symptoms related to long COVID. This paper discusses the potential application value of acupoint stimulation in the treatment of long COVID-related symptoms, based on the common sequelae of various systems involved in long COVID, and the effect of acupoint stimulation in the treatment of similar symptoms and diseases in recent years.

[Effect of transcutaneous auricular vagus nerve stimulation on the splenic α7nAchR/JAK2/STAT3 signaling pathway in LPS-induced depressive-like behavior rats].

OBJECTIVE: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the improvement of depressive-like behavior and the splenic α7 nicotinic acetylcholine receptor (α7nAchR) / Janus kinase 2 (JAK2 / signal transducer and activator of transcription 3 (STAT3) signaling pathway in lipopolysaccharide (LPS)-induced depressive-like behavior rats, so as to investigate the antidepressant mechanism of taVNS. METHODS: SD rats were randomly divided into SD control group, SD model group and SD taVNS group, and α7nAchR knockout rats were also randomly divided into α7 control group, α7 model group and α7 taVNS group, with 6 rats in each group. Rat model of depressive-like behavior was established by intraperitoneal injection of LPS (1 mg/kg). Rats in both SD taVNS and α7 taVNS groups received taVNS intervention once a day (2 Hz/15 Hz, 2 mA, 30 min) from 7 days before LPS injection to 2 days after LPS injection, respectively. The mean speed, activity time and side immobility time in the open field test were recorded after taVNS. The contents of interleukin 10 (IL-10) and chemokine (C-X-C motif) ligand 1 (CXCL1) in serum were detected by electrochemiluminescence multifactorial method. The splenic phosphorylated (p)-JAK2 and p-STAT3 protein expressions were detected by Western blot. RESULTS: Compared with their respective control groups, the mean speed and active time were reduced (P<0.01, P<0.05, P<0.001) and the side immobility time was increased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels were up-regulated (P<0.01, P<0.05, P<0.001), and splenic p-JAK2 protein expressions were down-regulated (P<0.05, P<0.01) in SD and α7nAchR knockout rats, and splenic p-STAT3 protein expression were down-regulated (P<0.05) in SD rats after LPS injection. Following taVNS intervention and in comparison with the model group , the mean speed and active time were increased (P<0.01) and the side immobility time was decreased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels down-regulated (P<0.05), while splenic p-JAK2 and p-STAT3 protein expressions were up-regulated (P<0.01, P<0.001) in the SD taVNS group rather than in the α7 taVNS group. Compared with SD taVNS group, the α7 taVNS group showed increased (P<0.001, P<0.05) side immobility time in the open field test and serum IL-10, decreased splenic p-JAK2 and p-STAT3 protein expressions (P<0.01, P<0.05). CONCLUSION: taVNS may exert anti-inflammatory effects through modulating the splenic α7nAchR/JAK2/STAT3 signaling pathway, thereby ameliorating LPS-induced depressive-like behavior in rats.

[Mechanism of melatonin-mediated antihyperglycemic effect of transcutaneous auricular vagus nerve stimulation].

OBJECTIVE: To observe the effects of transcutaneous auricular vagus nerve stimulation （taVNS） on plasma melatonin （MLT） content and insulin receptor expression in the liver, the skeletal muscles, and the pancreas of Zucker diabetic fatty （ZDF） rats, so as to explore the hypoglycemic mechanism of taVNS. METHODS: Thirty male ZDF rats were randomly divided into model group, taVNS group and sham-taVNS group, with 10 rats in each group； besides, 10 male Zucker lean rats of the same strain were collected for the blank control group. ZDF rats were fed with high-fat diet to induce type 2 diabetes mellitus （T2DM） rat model. In the taVNS group, HANS-100A electroacupuncture instrument was used to stimulate the cavum conchae of both sides. The stimulation sites of rats in the sham-taVNS were the same as the taVNS group, but without electricity delivered. The above interventions were performed 30 min each time, once daily, lasting for 6 weeks. Fasting blood glucose （FBG） was measured weekly in each group, the plasma metatonin （MLT） content was detected by ELISA, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was determined by Western blot. RESULTS: Compared with the blank control group, the level of FBG of rats were increased （P<0.01）, the plasma MLT content was decreased （P<0.01） and the insulin receptor expression level in the pancreatic tissue was decreased （P<0.01） in the model group. In the taVNS gruop, FBG was decreased （P<0.05, P<0.01）, the plasma MLT content was increased （P<0.01）, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was increased （P<0.05, P<0.01, P<0.001） when compared with the model group. Compared with the taVNS group, FBG was increased （P<0.05, P<0.01）, the plasma MLT content was decreased （P<0.01）, and the expression level of insulin receptors in the skeletal muscle and the pancreas was decreased （P<0.01, P<0.001） in the sham-taVNS group. CONCLUSION: The taVNS can improve the insulin resistance and ultimately obtain the antihyperglycemic effect through regulating MLT concentration.

Seasonal differences of feeding ecology of Uroteuthis edulis in the East China Sea based on fatty acid and stable isotope.

Uroteuthis edulis, an important fishery target species, plays an important role in the food web of the East China Sea. We collected U. edulis samples in the East China Sea from September 2020 to January 2021 to examine their feeding differences in autumn and winter based on fatty acid and stable isotope analyses. The results showed that the content of polyunsaturated fatty acids (PUFA) was the highest, followed by saturated fatty acids (SFA), and the lowest content of monounsaturated fatty acids (MUFA) in autumn and winter. Results of the similarity ana-lysis showed significant differences in PUFA and MUFA contents but no differences in SFA contents between autumn and winter. Results of non-metric multidimensional scale analysis showed that C18:1n9 could be used as signature fatty acids in autumn samples and C22:6n3 as characteristic fatty acids in winter samples. There was significant difference of δ15N between autumn and winter, but no difference of δ13C. The total area (TA), range of δ15N (NR), standard ellipse area (SEA) and the corrected version of the standard ellipse area (SEAC) in autumn were all smaller than those in winter, but range of δ13C (CR) was on the contrary. Results of the Spearman rank correlation test showed that there were differences between fatty acid content and stable isotope ratio of U. edulis and the dorsal mantle length in autumn and winter. Our results could provide basic data for understanding material and energy flow of the East China Sea food web, which is conducive to the sustainable development and utilization of U. edulis.