Bibliometric analysis of electroencephalogram research in mild cognitive impairment from 2005 to 2022.

Background: Electroencephalogram (EEG), one of the most commonly used non-invasive neurophysiological examination techniques, advanced rapidly between 2005 and 2022, particularly when it was used for the diagnosis and prognosis of mild cognitive impairment (MCI). This study used a bibliometric approach to synthesize the knowledge structure and cutting-edge hotspots of EEG application in the MCI. Methods: Related publications in the Web of Science Core Collection (WosCC) were retrieved from inception to 30 September 2022. CiteSpace, VOSviewer, and HistCite software were employed to perform bibliographic and visualization analyses. Results: Between 2005 and 2022, 2,905 studies related to the application of EEG in MCI were investigated. The United States had the highest number of publications and was at the top of the list of international collaborations. In terms of total number of articles, IRCCS San Raffaele Pisana ranked first among institutions. The Clinical Neurophysiology published the greatest number of articles. The author with the highest citations was Babiloni C. In descending order of frequency, keywords with the highest frequency were "EEG," "mild cognitive impairment," and "Alzheimer's disease". Conclusion: The application of EEG in MCI was investigated using bibliographic analysis. The research emphasis has shifted from examining local brain lesions with EEG to neural network mechanisms. The paradigm of big data and intelligent analysis is becoming more relevant in EEG analytical methods. The use of EEG to link MCI to other related neurological disorders, and to evaluate new targets for diagnosis and treatment, has become a new research trend. The above-mentioned findings have implications in the future research on the application of EEG in MCI.

Manual acupuncture at ST36 attenuates rheumatoid arthritis by inhibiting M1 macrophage polarization and enhancing Treg cell populations in adjuvant-induced arthritic rats.

OBJECTIVES: Acupuncture has been found to be effective at relieving many inflammatory pain conditions, including rheumatoid arthritis (RA). We aimed to assess the anti-inflammatory potential of manual acupuncture (MA) treatment of RA using adjuvant-induced arthritic (AIA) rats and to explore the underlying mechanisms. METHODS: The anti-inflammatory and analgesic actions of MA at ST36 (Zusanli) in AIA rats were assessed using paw withdrawal latency and swelling, histological examination and cytokine detection by enzyme-linked immunoassay (ELISA). The cell-cell communication (CCC) network was analyzed with a multiplex immunoassay of 24 immune factors expressed in the inflamed joints, and the macrophage and Treg populations and associated cytokines regulated by MA were investigated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), ELISA and flow cytometry. RESULTS: MA markedly decreased heat hyperalgesia and paw swelling in AIA rats. MA-treated rats also exhibited decreased levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß) coupled with increased anti-inflammatory cytokines (IL-10, transforming growth factor (TGF)-ß1) in the ankle joints at protein and mRNA levels. CCC network analysis confirmed that macrophages are of critical importance and are potential therapeutic targets in RA. Repeated treatment with MA triggered a macrophage phenotypic switch in the paws, with fewer M1 macrophages. Prominent increases in the Treg cell population and TGF-ß1 in the popliteal lymph nodes demonstrated the immunomodulatory effects of MA. Furthermore, a selective TGF-ß1-receptor inhibitor, SB431542, attenuated the anti-inflammatory effects of MA and MA-induced suppression of the levels of M1-released cytokines. CONCLUSION: These findings provide novel evidence that the anti-inflammatory and analgesic effects of MA on RA act through phenotypic modulation involving the inhibition of M1 macrophage polarization and an increase in the Treg cell population, highlighting the potential therapeutic advantages of acupuncture in controlling pain and ameliorating inflammatory conditions.

Alteration of network connectivity in stroke patients with apraxia of speech after tDCS: A randomized controlled study.

Objective: This study aimed to examine the changes in the functional connectivity of the cortical speech articulation network after anodal transcranial direct current stimulation (A-tDCS) over the left lip region of the primary motor cortex (M1) in subacute post-stroke patients with apraxia of speech (AoS), and the effect of A-tDCS on AoS. Methods: A total of 24 patients with post-stroke AoS were randomized into two groups and received A-tDCS over the left lip region of M1 (tDCS group)/ sham tDCS (control group) as well as speech and language therapy two times per day for 5 days. Before and after the treatment, the AoS assessments and electroencephalogram (EEG) were evaluated. The cortical interconnections were measured using the EEG non-linear index of cross approximate entropy (C-ApEn). Results: The analysis of EEG showed that, after the treatment, the activated connectivity was all in the left hemisphere, and not only regions in the speech articulation network but also in the dorsal lateral prefrontal cortex (DLPFC) in the domain-general network were activated in the tDCS group. In contrast, the connectivity was confined to the right hemisphere and between bilateral DLPFC and bilateral inferior frontal gyrus (IFG) in the control group. In AoS assessments, the tDCS group improved significantly more than the control group in four of the five subtests. The results of multivariate linear regression analyses showed that only the group was significantly associated with the improvement of word repetition (P = 0.002). Conclusion: A-tDCS over the left lip region of M1 coupled with speech therapy could upregulate the connectivity of both speech-specific and domain-general networks in the left hemisphere. The improved articulation performance in patients with post-stroke AoS might be related to the enhanced connectivity of networks in the left hemisphere induced by tDCS. Clinical trial registration: ChiCTR-TRC-14005072.

tDCS-EEG for Predicting Outcome in Patients With Unresponsive Wakefulness Syndrome.

Objectives: We aimed to assess the role of transcranial direct current stimulation (tDCS) combined with electroencephalogram (EEG) for predicting prognosis in UWS cases. Methods: This was a historical control study that enrolled 85 patients with UWS. The subjects were assigned to the control (without tDCS) and tDCS groups. Conventional treatments were implemented in both the control and tDCS groups, along with 40 multi-target tDCS sessions only in the tDCS group. Coma Recovery Scale-Revised (CRS-R) was applied at admission. The non-linear EEG index was evaluated after treatment. The modified Glasgow Outcome Scale (mGOS) was applied 12 months after disease onset. Results: The mGOS improvement rate in the tDCS group (37.1%) was higher than the control value (22.0%). Linear regression analysis revealed that the local and remote cortical networks under unaffected pain stimulation conditions and the remote cortical network under affected pain stimulation conditions were the main relevant factors for mGOS improvement. Furthermore, the difference in prefrontal-parietal cortical network was used to examine the sensitivity of prognostic assessment in UWS patients. The results showed that prognostic sensitivity could be increased from 54.5% (control group) to 84.6% (tDCS group). Conclusions: This study proposes a tDCS-EEG protocol for predicting the prognosis of UWS. With multi-target tDCS combined with EEG, the sensitivity of prognostic assessment in patients with UWS was improved. The recovery might be related to improved prefrontal-parietal cortical networks of the unaffected hemisphere.

Multi-Target and Multi-Session Transcranial Direct Current Stimulation in Patients With Prolonged Disorders of Consciousness: A Controlled Study.

Objectives: To investigate the effect of multi-session transcranial direct current stimulation (tDCS) over the prefrontal area, left dorsolateral prefrontal cortex (DLPFC), and bilateral fronto-temporo-parietal cortices (FTPCs) in patients with prolonged disorders of consciousness (DOC) and to examine the altered cortical interconnections using non-linear electroencephalography (EEG). Methods: In this open-label controlled study, conventional treatments were implemented in both the control and tDCS groups, together with 80 tDCS sessions only in the tDCS group. The order of tDCS targets was as follows: prefrontal area, left FTPC, right FTPC, and left DLPFC. The Coma Recovery Scale-Revised (CRS-R) and non-linear EEG index were evaluated before and after the treatment. Additionally, the modified Glasgow Outcome Scale (mGOS) was used as a follow-up evaluation at 12 months after the disease onset. Results: The CRS-R improved significantly in both groups after the treatment. However, the CRS-R and mGOS were more significantly improved in the tDCS group than in the control group. Among the cross approximate entropy (C-ApEn) indices, the local CA-PA and CA-FA under the affected painful stimulus condition and all local and remote indices of the unaffected side under the unaffected painful stimulus condition were significantly higher in the tDCS group than in the control group. Multivariate logistic regression analysis revealed that group and type were the main relevant factors based on mGOS improvement. Multivariate linear regression analysis revealed that group, CA-FA, and CU-MTU were the main relevant factors based on CRS-R improvement under the affected painful stimulus conditions, whereas only CU-MTU and CU-FPU were relevant under the unaffected painful stimulus condition. Conclusion: Multi-target and multi-session tDCS could improve the cortical connections between the primary sensorimotor and frontal cortices of the affected hemisphere and the prefrontal-parietal and temporo-parietal associative cortical networks of the unaffected hemisphere. Thus, this tDCS protocol may be used as an add-on treatment for prolonged DOC.

Outcome Prediction in Unresponsive Wakefulness Syndrome and Minimally Conscious State by Non-linear Dynamic Analysis of the EEG.

Objectives: This study aimed to investigate the role of non-linear dynamic analysis (NDA) of the electroencephalogram (EEG) in predicting patient outcome in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Methods: This was a prospective longitudinal cohort study. A total of 98 and 64 UWS and MCS cases, respectively, were assessed. During admission, EEGs were acquired under eyes-closed and pain stimulation conditions. EEG nonlinear indices, including approximate entropy (ApEn) and cross-ApEn, were calculated. The modified Glasgow Outcome Scale (mGOS) was employed to assess functional prognosis 1 year following brain injury. Results: The mGOS scores were improved in 25 (26%) patients with UWS and 42 (66%) with MCS. Under the painful stimulation condition, both non-linear indices were lower in patients with UWS than in those with MCS. The frontal region, periphery of the primary sensory area (S1), and forebrain structure might be the key points modulating disorders of consciousness. The affected local cortical networks connected to S1 and unaffected distant cortical networks connecting S1 to the prefrontal area played important roles in mGOS score improvement. Conclusions: NDA provides an objective assessment of cortical excitability and interconnections of residual cortical functional islands. The impaired interconnection of the residual cortical functional island meant a poorer prognosis. The activation in the affected periphery of the S1 and the increase in the interconnection of affected local cortical areas around the S1 and unaffected S1 to the prefrontal and temporal areas meant a relatively favorable prognosis.

Study on Typical Diarylurea Drugs or Derivatives in Cocrystallizing with Strong H-Bond Acceptor DMSO.

Diarylureas are widely used in self-assembly and supramolecular chemistry owing to their outstanding characteristics as both H-bond donors and acceptors. Unfortunately, this bonding property is rarely applied in the development of urea-containing drugs. Herein, seven related dimethyl sulfoxide (DMSO) complexes were screened from 12 substrates involving sorafenib and regorafenib, mainly considering the substitution effect following a robust procedure. All complexes were structurally confirmed by spectroscopic means and thermal analysis. Specially, five cocrystals with three deuterated, named sorafenib·DMSO, donafenib·DMSO, deuregorafenib·DMSO, 6·DMSO, and 7·DMSO were obtained. The crystal structures revealed that all host molecules consistently bonded with DMSO in intermolecular interaction in a 1:1 stoichiometry. However, further comparison with documented DMSO complexes and parent motifs presented some arrangement diversities especially for 6·DMSO which offered a counter-example to previous rules. Major changes in the orientation of meta-substituents and the packing stability for sorafenib·DMSO and deuregorafenib·DMSO were rationalized by theory analysis and computational energy calculation. Cumulative data implied that the planarization of two aryl planes in diarylureas may play a crucial role in cocrystallization. Also, a polymorph study bridged the transformation between these ureas and their DMSO complexes.

Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway.

OBJECTIVE: To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. METHODS: Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. RESULTS: Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05). CONCLUSIONS: Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

Transcranial Direct Current Stimulation Over Prefrontal Areas Improves Psychomotor Inhibition State in Patients With Traumatic Brain Injury: A Pilot Study.

OBJECTIVES: Many post-traumatic patients with minimally conscious state are complicated by psychomotor inhibition state (PIS), which impedes further rehabilitation. The treatment of PIS is not satisfactory. This pilot study aimed to investigate effects of anodal transcranial direct current stimulation (A-tDCS) on PIS in post-traumatic patients and examine the altered cortical activation after tDCS using non-linear electroencephalogram (EEG). METHODS: The study included 10 patients with post-traumatic PIS. An A-B design was used. The patients received 4 weeks of sham tDCS during Phase A, and they received A-tDCS over the prefrontal area and left dorsolateral prefrontal cortex (DLPFC) for 4 weeks (40 sessions) during Phase B. Conventional treatments were administered throughout both phases. JFK Coma Recovery Scale-Revised (CRS-R), apathy evaluation scale (AES), and the EEG non-linear indices of approximate entropy (ApEn) and cross approximate entropy (C-ApEn) were measured before Phase A, before Phase B, and after Phase B. RESULTS: After A-tDCS treatment, CRS-R and AES were improved significantly. ApEn and C-ApEn results showed that the local cortical connection of bilateral sensorimotor areas with their peripheral areas could be activated by affected painful stimuli, while bilateral cerebral hemispheres could be activated by the unaffected painful-stimuli condition. Linear regression analysis revealed that the affected sensorimotor cortex excitability and unaffected local and distant cortical networks connecting the sensorimotor area to the prefrontal area play a major role in AES improvement. CONCLUSION: A-tDCS over the prefrontal area and left DLPFC improves PIS. The recovery might be related to increased excitability in local and distant cortical networks connecting the sensorimotor area to the prefrontal area. Thus, tDCS may be an alternative treatment for post-traumatic PIS.

P2RX7 in Dopaminergic Neurons of Ventral Periaqueductal Gray Mediates HTWP Acupuncture-Induced Consciousness in Traumatic Brain Injury.

The induction of a coma by traumatic brain injury (TBI) is a crucial factor for poor clinical prognoses. We report that acupuncture at the hand 12 Jing-Well points (HTWP) improved consciousness and neurologic function in TBI rats. Gene chip analyses showed that HTWP acupuncture mostly activated genes modulating neuronal projections (P2rx7, P2rx3, Trpv1, Tacr1, and Cacna1d), protein secretion (Exoc1, Exoc3l1, Fgb, and Fgr), and dopamine (DA) receptor D3 (Drd3) in the ventral periaqueductal gray (vPAG), among which the expression rate of P2rx7 was the most obviously increased. Acupuncture also increased the expression and excitability of DA and P2RX7 neurons, and the DA neurons expressed P2RX7, P2RX3, and TRPV1 in the vPAG. Intracerebroventricular administration of P2RX7, P2RX3, or TRPV1 antagonists blocked acupuncture-induced consciousness, and the subsequent injection of a P2RX7 antagonist into the vPAG nucleus also inhibited this effect. Our findings provide evidence that acupuncture alleviates TBI-induced comas via DA neurons expressing P2RX7 in the vPAG, so as to reveal the cellular and molecular mechanisms of the improvement of TBI clinical outcomes by HTWP acupuncture.

[Research advances in the clinical effect of bloodletting puncture at well-points in treatment of acute central nervous injury].

Bloodletting puncture at twelve well-points is a characteristic emergency therapy in traditional Chinese medicine. This article reviewed the research advances in the clinical effect of this therapy in the treatment of acute central nervous injury and its mechanism of action over the past 30 years, and it is found that this therapy can effectively improve disturbance of consciousness, neurological defects, and cerebral edema caused by stroke, traumatic brain injury, and carbon monoxide poisoning. The mechanism involves the improvement of cerebral blood flow and tissue oxygen supply, repair of the blood-brain barrier, and regulation of local ion balance. Well-designed clinical trials and in-depth research on biological mechanisms should be performed in future to promote and guide its clinical application.

Neurophysiology and Treatment of Disorders of Consciousness Induced by Traumatic Brain Injury: Orexin Signaling as a Potential Therapeutic Target.

BACKGROUND: Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. However, the effectiveness of drugs targeting ARAS activation is still inadequate, and novel therapeutic modalities are urgently needed. METHODS: The goal of this work is to describe the neural loops of wakefulness, and explain how these elements participate in DOC, with emphasis on the identification of potential new therapeutic options for DOC induced by TBI. RESULTS: Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, the posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field. CONCLUSION: The hypothalamic-centered orexin has been adopted as the point of entry into the system of consciousness control, and modulators of orexin signaling opened several therapeutic opportunities for the treatment of DOC.

Exendin-4 promotes actin cytoskeleton rearrangement and protects cells from Nogo-A-Δ20 mediated spreading inhibition and growth cone collapse by down-regulating RhoA expression and activation via the PI3K pathway.

Exendin-4 is a protein of the GLP-1 family currently used to treat diabetes. Recently, a greater number of biological properties have been associated with the GLP-1 family. Our data shows that exendin-4 treatment significantly increases the cytoskeleton rearrangement, which leads to an increasingly differentiated phenotype and reduced cell migration. We also found that exendin-4 could prevent SH-SY5Y and PC12 cells from Nogo-A-Δ20 mediated spreading inhibition and neurite collapse. Western blot analysis indicated that exendin-4 treatment both reduced the expression and activation of RhoA via the PI3K signaling pathway. These data suggest that exendin-4 may protect nerve regeneration by preventing the inhibition of Nogo-A via down-regulating RhoA expression and activation.

Acupuncture Alleviates Rheumatoid Arthritis by Immune-Network Modulation.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory and debilitating disease that involves the systemic imbalance of the immune network. Previous studies have shown that acupuncture can help treat RA. However, its specific mechanisms are not fully understood. Thus, the present study was designed to clarify the mechanisms of acupuncture acted on RA via immune network modulation using complete Freund's adjuvant (CFA)-induced arthritic rats. Results revealed that manual acupuncture (MA) could alleviate the inflammation and pain of infected joints. Moreover, MA could effectively stimulate the innate immune cytokines (IL-1[Formula: see text], IL-1[Formula: see text], IL-6, IL-7, IL-18, TNF-[Formula: see text]) and adaptive immunity cytokines (IL-2, IL-12, IFN-[Formula: see text], IL-4, IL-5, IL-10, IL-13, IL-17) as the main part of the immune response and repaired damage of RA. These complex immunomodulatory processes were analyzed quantitatively by cell-cell communication (CCC) networks. The CCC networks demonstrated that the immune networks were enhanced with the development of RA, while MA enhanced the immune networks in the early stage to act on RA and promoted the immune-network to a normal level at the late stage. Moreover, we found that monocyte/macrophage and endothelial cells were the key cells of innate immunity and body cells; TH1, TH2 and B cells were the key cells of adaptive immunity, which were also the main target cells for MA regulation.

Challenges and research progress of the use of mesenchymal stem cells in the treatment of ischemic stroke.

Cerebral Ischemic Stroke (CIS) has become a hot issue in medical research because of the diversity of risk factors and the uncertainty of prognosis. In the field of regenerative medicine, mesenchymal stem cells (MSCs) have an increasingly prominent position due to their advantages of multiple differentiation, low immunogenicity and wide application. In the basic and clinical research of CIS, there are still some problems to be solved in the treatment of CIS. This paper will discuss the progresses and some obstacles of current MSCs for the treatment of CIS.

[Professor ZHENG Kuishan's experience in the clinical treatment of bi syndrome with acupuncture and moxibustion].

Professor ZHENG Kuishan has been engaged in the education and clinical practice of acupuncture and moxibustion for over 60 years. Professor ZHENG is strict in scholarly research and exquisite in medical techniques and he is good at treatment of bi syndrome induced by invasion of wind, cold and damp with warming and, promoting therapy. He emphasizes on syndrome differentiation and acupoint combination and selects the accurate manipulations. Not only are the symptoms relieved apparently, but also the body state is improved. As a result, the primary and secondary are treated simultaneously. In the paper, professor ZHENG's experience is introduced in the treatment of bi syndrome in the aspects of theory, method, formula, acupoint and technique. And his clinical therapeutic approaches have been deeply analyzed.

Efficacy and safety of electroacupuncture with different acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. METHODS/DESIGN: This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. DISCUSSION: The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. TRIAL REGISTRATION: The register number of randomized controlled trial is NCT02195908 . The date of registration was 21 July 2014.