Cathodal bilateral transcranial direct-current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia-reperfusion injury.

Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.

Acupuncture for obesity and related diseases: Insight for regulating neural circuit.

Obesity is defined as abnormal or excessive fat accumulation that may impair health. Obesity is associated with numerous pathological changes including insulin resistance, fatty liver, hyperlipidemias, and other obesity-related diseases. These comorbidities comprise a significant public health threat. Existing anti-obesity drugs have been limited by side effects that include depression, suicidal thoughts, cardiovascular complications and stroke. Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions, while avoiding side effects. However, the mechanisms of acupuncture in treating obesity-related diseases, especially its effect on neural circuits, are not well understood. A growing body of research has studied acupuncture's effects on the endocrine system and other mechanisms related to the regulation of neural circuits. In this article, recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system, as well as some neural circuits involved, was summarized. Based on this, acupuncture's potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed, leading to a deeper mechanistic understanding of acupuncture's effects and providing insight and direction for future research about obesity. Please cite this article as: Jiang LY, Tian J, Yang YN, Jia SH, Shu Q. Acupuncture for obesity and related diseases: insight for regulating neural circuit. J Integr Med. 2024; 22(2): 93-101.

Neural correlates of cognitive behavioral therapy-based interventions for bipolar disorder: A scoping review.

Cognitive Behavioral Therapy (CBT) is among the gold-standard psychotherapeutic interventions for the treatment of psychiatric disorders, including bipolar disorder (BD). While the clinical response of CBT in patients with BD has been widely investigated, its neural correlates remain poorly explored. Therefore, this scoping review aimed to discuss neuroimaging studies on CBT-based interventions in bipolar populations. Particular attention has been paid to similarities and differences between studies to inform future research. The literature search was conducted on PubMed, PsycINFO, and Web of Science databases in June 2023, identifying 307 de-duplicated records. Six studies fulfilled the inclusion criteria and were reviewed. All of them analyzed functional brain activity data. Four studies showed that the clinical response to CBT was associated with changes in the functional activity and/or connectivity of prefrontal and posterior cingulate cortices, temporal parietal junction, amygdala, precuneus, and insula. In two additional studies, a peculiar pattern of baseline activations in the prefrontal cortex, hippocampus, amygdala, and insula predicted post-treatment improvements in depressive symptoms, emotion dysregulation, and psychosocial functioning, although CBT-specific effects were not shown. These results suggest, at the very preliminary level, the potential of CBT-based interventions in modulating neural activity and connectivity of patients with BD, especially in regions ascribed to emotional processing. Nonetheless, the discrepancies between studies concerning aims, design, sample characteristics, and CBT and fMRI protocols do not allow conclusions to be drawn. Further research using multimodal imaging techniques, better-characterized BD samples, and standardized CBT-based interventions is needed.

Red ginseng ameliorates lipotoxicity-induced renal fibrosis in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. AIM OF THE STUDY: This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. MATERIALS AND METHODS: A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-ß1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RESULTS: RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-ß1, and α-SMA, and up-regulated OAT1 and E-cadherin. CONCLUSIONS: RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis.

Synergistic amelioration between Ligusticum striatum DC and borneol against cerebral ischemia by promoting astrocytes-mediated neurogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Amplitude Adaptive Modulation of Neural Oscillations Over Long-Term Dynamic Conditions: A Computational Study.

Closed-loop deep brain stimulation (DBS) shows great potential for precise neuromodulation of various neurological disorders, particularly Parkinson's disease (PD). However, substantial challenges remain in clinical translation due to the complex programming procedure of closed-loop DBS parameters. In this study, we proposed an online optimized amplitude adaptive strategy based on the particle swarm optimization (PSO) and proportional-integral-differential (PID) controller for modulation of the beta oscillation in a PD mean field model over long-term dynamic conditions. The strategy aimed to calculate the stimulation amplitude adapting to the fluctuations caused by circadian rhythm, medication rhythm, and stochasticity in the basal ganglia-thalamus-cortical circuit. The PID gains were optimized online using PSO, based on modulation accuracy, mean stimulation amplitude, and stimulation variation. The results showed that the proposed strategy optimized the stimulation amplitude and achieved beta power modulation under the influence of circadian rhythm, medication rhythm, and stochasticity of beta oscillations. This work offers a novel approach for precise neuromodulation with the potential for clinical translation.

A simple technical innovation to prevent needle stick injuries among dental professionals.

OBJECTIVE: Dental healthcare personnel face the potential danger of being exposed to infectious patients while administering local anesthesia injections during dental operations. This could lead to unintentional transfer of infectious diseases from patients to physicians. Although safety measures such as the One-hand-scoop technique and the use of safety syringes, plastic needle cap holders, and needles with safety caps are in place, there have been instances of needle stick injuries reported in clinics. This might be due to the lack of adherence to conventional safety measures or the impracticality of safety techniques and safety syringes. This article aims to demonstrate the utilization of dental tweezers, specifically London College tweezers or dental forceps, for the secure recapping of needles, eliminating the requirement for extra equipment or devices. SUBJECTS AND METHODS: After obtaining ethical approval (Approval No.: 024-01-2024) from the College of Dentistry, Dar Al Uloom University, 67 dental professionals, with consent for participation in the study, were included. They were requested to use dental tweezers/London College tweezers and dental extraction forceps such as maxillary anterior, mandibular anterior, and maxillary bayonet root forceps individually to recap the local anesthetic needles. The efficacy of these techniques was evaluated against the one-hand scoop technique for its ease, convenience, and reliability in preventing needle stick injuries. RESULTS: The evaluation of dental professionals regarding the ease of using dental tweezers to recap needles, compared to the one-hand scoop technique (p=0.592), maxillary bayonet root forceps (p=0.746), mandibular anterior forceps (p=0.380), and maxillary anterior forceps (p=0.808), did not yield statistically significant results. The assessment of the procedural simplicity of the one-hand scoop technique showed a satisfaction rate of over 40%, whereas the application of dental tweezers resulted in a satisfaction rate of 30%. However, the use of dental tweezers for needle recapping resulted in a satisfaction rate of over 50%, compared to a satisfaction rate of 30% for the one-handed scoop technique. CONCLUSIONS: There is no statistically significant difference in the assessment of the efficacy of dental tweezers and the one-hand scoop technique, bayonet root forceps, mandibular anterior forceps, maxillary anterior forceps, and dental tweezers for the needle capping technique. Therefore, dental forceps can be used instead of the one-handed scoop approach. The needle recapping procedure outlined in our study, aimed at preventing needle stick injuries, is simple to implement, and all dental specialties have convenient access to the required instruments.

Leaf Extract from European Olive (Olea europaea L.) Post-Transcriptionally Suppresses the Epithelial-Mesenchymal Transition and Sensitizes Gastric Cancer Cells to Chemotherapy.

The overall survival of patients with the advanced and recurrent gastric cancer (GC) remains unfavorable. In particular, this is due to cancer spreading and resistance to chemotherapy associated with the epithelial-mesenchymal transition (EMT) of tumor cells. EMT can be identified by the transcriptome profiling of GC for EMT markers. Indeed, analysis of the TCGA and GTEx databases (n = 408) and a cohort of GC patients (n = 43) revealed that expression of the CDH2 gene was significantly decreased in the tumors vs. non-tumor tissues and correlated with the overall survival of GC patients. Expression of the EMT-promoting transcription factors SNAIL and ZEB1 was significantly increased in GC. These data suggest that targeting the EMT might be an attractive therapeutic approach for patients with GC. Previously, we demonstrated a potent anti-cancer activity of the olive leaf extract (OLE). However, its effect on the EMT regulation in GC remained unknown. Here, we showed that OLE efficiently potentiated the inhibitory effect of the chemotherapeutic agents 5-fluorouracil (5-FU) and cisplatin (Cis) on the EMT and their pro-apoptotic activity, as was demonstrated by changes in the expression of the EMT markers (E- and N-cadherins, vimentin, claudin-1) in GC cells treated with the aforementioned chemotherapeutic agents in the presence of OLE. Thus, culturing GC cells with 5-FU + OLE or Cis + OLE attenuated the invasive properties of cancer cells. Importantly, upregulation of expression of the apoptotic markers (PARP cleaved form) and increase in the number of cells undergoing apoptosis (annexin V-positive) were observed for GC cells treated with a combination of OLE and 5-FU or Cis. Collectively, our data illustrate that OLE efficiently interferes with the EMT in GC cells and potentiates the pro-apoptotic activity of certain chemotherapeutic agents used for GC therapy.

Fractal Phototherapy in Maximizing Retina and Brain Plasticity.

The neuroplasticity potential is reduced with aging and impairs during neurodegenerative diseases and brain and visual system injuries. This limits the brain's capacity to repair the structure and dynamics of its activity after lesions. Maximization of neuroplasticity is necessary to provide the maximal CNS response to therapeutic intervention and adaptive reorganization of neuronal networks in patients with degenerative pathology and traumatic injury to restore the functional activity of the brain and retina.Considering the fractal geometry and dynamics of the healthy brain and the loss of fractality in neurodegenerative pathology, we suggest that the application of self-similar visual signals with a fractal temporal structure in the stimulation therapy can reactivate the adaptive neuroplasticity and enhance the effectiveness of neurorehabilitation. This proposition was tested in the recent studies. Patients with glaucoma had a statistically significant positive effect of fractal photic therapy on light sensitivity and the perimetric MD index, which shows that methods of fractal stimulation can be a novel nonpharmacological approach to neuroprotective therapy and neurorehabilitation. In healthy rabbits, it was demonstrated that a long-term course of photostimulation with fractal signals does not harm the electroretinogram (ERG) and retina structure. Rabbits with modeled retinal atrophy showed better dynamics of the ERG restoration during daily stimulation therapy for a week in comparison with the controls. Positive changes in the retinal function can indirectly suggest the activation of its adaptive plasticity and the high potential of stimulation therapy with fractal visual stimuli in a nonpharmacological neurorehabilitation, which requires further study.

Chloroprocaine 3% Gel as a Novel Ocular Topical Anesthetic: Results from a Multicenter, Randomized Clinical Trial in Patients Undergoing Cataract Surgery.

Purpose: To compare the efficacy and safety of a novel ophthalmic anesthetic, chloroprocaine 3% gel to tetracaine 0.5% eye drops in patients undergoing cataract surgery with phacoemulsification. Methods: This was a prospective, randomized, multicenter, active-controlled, masked-observer, parallel group competitive equivalence study. The study comprised 338 patients having routine cataract extraction by clear corneal phacoemulsification, randomized to receive 3 drops of chloroprocaine gel (n = 166) or tetracaine eye drops (n = 172) before surgery. The primary objective of the study was to assess the equivalence of chloroprocaine gel to tetracaine eye drops as proportion of patients with successful ocular surface anesthesia, without any supplementation just before intraocular lens implantation. Safety measurements were pain, irritation, burning, stinging, photophobia, and foreign body sensation, graded by the patient and objective ocular signs. Results: Equivalence was demonstrated, with a somewhat higher success rate of chloroprocaine gel: 152/166 (92.0%) chloroprocaine versus 153/172 (90.5%) tetracaine patients achieved ocular surface anesthesia with no supplementation. Difference in proportions was 1.5% confidence interval [95% CI: (-3.6 to 6.6)] and 90% CI fell within (-10 to 10). Mean onset of anesthesia was 1.35 ± 0.87 min for chloroprocaine and 1.57 ± 1.85 for tetracaine (P = 0.083). Mean duration of anesthesia was 21.57 ± 12.26 min for chloroprocaine and 22.04 ± 12.58 for tetracaine (P = 0.574). No treatment emergent adverse events related to chloroprocaine were reported and no relevant findings related to local tolerance or vital signs were observed in both arms. Conclusions: Results obtained from the present cataract study demonstrated that chloroprocaine 3% ophthalmic gel is safe and effective, representing a valid alternative in ocular topical anesthesia. Clinical Trial Registration number: NCT04685538.

Adjunctive Effect of Photobiomodulation Therapy with Nd:YAG Laser in the Treatment of Inferior Alveolar Nerve Paresthesia.

Background: Disruption of peripheral branches of the trigeminal nerve in the field of maxillofacial surgery is a known risk due to the close connection of these branches with the bony structures of the maxilla and mandible. As a result, injuries of the lingual nerve and inferior alveolar nerve take place within routine maxillofacial surgery procedures, including local anesthetic injection, wisdom tooth surgery, and dental implant placement, resulting in paresthesia and dysesthesia. During the last three decades, low-level lasers (LLL) have been frequently used in various medical fields. Lately, this application has increased in several sectors. Methods and materials: This experiment was designed to explore the effect of low-level laser therapy (LLLT) with Nd:YAG on the paresthesia and dysesthesia of the lower lip. This ethics committee of Tbzmed, Tabriz, Iran, proved the present experiment with ethical code: IR.TBZMED.REC.1401.839. Results: After completing 10 sessions of laser therapy for the case group consisting of 25 patients with lower lip anesthesia, the visual analog scale index results revealed that following six sessions of laser therapy, a significant difference appeared in contrast to the control group. Also, according to the two-point tests, significant difference among the experimental and the control group appeared after ninth session of the laser therapy. Conclusions: Altogether, these data suggested LLLT with Nd:YAG as an effective treatment option for decreasing the anesthesia of the lower lip.

Exploring the mechanisms of kaempferol in neuroprotection: Implications for neurological disorders.

Kaempferol, a flavonoid compound found in various fruits, vegetables, and medicinal plants, has garnered increasing attention due to its potential neuroprotective effects in neurological diseases. This research examines the existing literature concerning the involvement of kaempferol in neurological diseases, including stroke, Parkinson's disease, Alzheimer's disease, neuroblastoma/glioblastoma, spinal cord injury, neuropathic pain, and epilepsy. Numerous in vitro and in vivo investigations have illustrated that kaempferol possesses antioxidant, anti-inflammatory, and antiapoptotic properties, contributing to its neuroprotective effects. Kaempferol has been shown to modulate key signaling pathways involved in neurodegeneration and neuroinflammation, such as the PI3K/Akt, MAPK/ERK, and NF-κB pathways. Moreover, kaempferol exhibits potential therapeutic benefits by enhancing neuronal survival, attenuating oxidative stress, enhancing mitochondrial calcium channel activity, reducing neuroinflammation, promoting neurogenesis, and improving cognitive function. The evidence suggests that kaempferol holds promise as a natural compound for the prevention and treatment of neurological diseases. Further research is warranted to elucidate the underlying mechanisms of action, optimize dosage regimens, and evaluate the safety and efficacy of this intervention in human clinical trials, thereby contributing to the advancement of scientific knowledge in this field.

Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis.

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45-64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65-74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

Moxibustion preconditioning reduces inflammatory response in rats with cerebral ischemia-reperfusion injury by regulating PI3K / AKT / mTOR signaling pathway. / 艾灸预处理通过调控PI3K/AKT/mTORä¿¡å·é€šè·¯å‡è½»è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç‚Žæ€§ååº”.

OBJECTIVES: To observe the effect of moxibustion preconditioning on inflammatory response in rats with cerebral ischemia reperfusion injury (CIRI), so as to explore its mechanisms underlying improving CIRI. METHODS: Seventy-five male SD rats were randomly divided into sham operation, model, moxibustion preconditioning 3 days (Moxi 1), moxibustion preconditioning 5 days (Moxi 2) and moxibustion preconditioning 7 days (Moxi 3) groups, with 15 rats in each group. Moxibustion was applied at "Baihui"(GV20), "Dazhui"(GV14) and "Zusanli"(ST36) for 20 min once a day, totally for 3, 5 or 7 days. Thirty minutes after the last moxibustion treatment, the CIRI model was established by occlusion of the middle cerebral artery. The neurological deficit score was assessed by using Longa's method. The infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The morphological changes of cortical neurons were observed by HE staining. The contents of inflammatory factors interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S-100ß protein (S-100ß) and neuron-specific enolase (NSE) were detected by ELISA. The expression of phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and mammalian target of rapamycin (mTOR) proteins in the ischemic cortex tissues were detected by immunohistochemistry and Western blot. RESULTS: Compared with the sham operation group, the neurological function score and the percentage of cerebral ischemic volume were increased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly increased (P<0.01), while the protein expressions of PI3K, p-PI3K, AKT and mTOR in the cerebral cortex were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function score and the percentage of cerebral ischemic volume were significantly decreased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly decreased (P<0.01), and the expressions of PI3K, p-PI3K, AKT and mTOR proteins in the cerebral cortex were significantly increased (P<0.01) in three moxibustion groups. Compared with the Moxi 1 and Moxi 2 groups, the above indicators were significantly improved in rats of the Moxi 3 group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion preconditioning can significantly improve the neurological function of rats after ischemia-reperfusion, inhibit serum inflammatory factors IL-1 ß and TNF-α, inhibit brain tissue injury markers S-100ß and NSE, which may be related to the activation of PI3K/AKT/mTOR signaling pathway. The protective effect of moxibustion preconditioning for 7 days on CIRI was better than that of 5 days and 3 days.

Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. / ç”µé’ˆå¯¹ç³–å°¿ç— è®¤çŸ¥åŠŸèƒ½éšœç¢å¤§é¼ PI3K/Akt/CREBä¿¡å·é€šè·¯å’Œæµ·é©¬ç¥žç»å ƒå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. METHODS: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. RESULTS: Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). CONCLUSIONS: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Effects of the elongated needling combined with routine acupuncture therapy in the patients with post-stroke hemiplegia and central pain： a randomized controlled trial. / èŠ’é’ˆé€åˆºè”åˆä½“é’ˆæ²»ç–—å¯¹ä¸­é£ŽåŽåç˜«ä¼´ä¸­æž¢æ€§ç–¼ç—›æ‚£è€ çš„ä¸´åºŠç–—æ•ˆè§‚å¯Ÿï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To investigate the effects of the elongated needling at the points of hand and foot yang meridians and the Governor Vessel combined with the routine acupuncture therapy on pain, balance function and muscle strength of the patients with post-stroke hemiplegia and central post-stroke pain (CPSP), and to investigate whether its therapeutic mechanism is related to antioxidant damage. METHODS: Ninety-four patients with post-stroke hemiplegia and CPSP admitted from March 2020 to September 2021 were divided into a trial group (47 cases, 1 cases dropped out) and a control group (47 cases 3 cases dropped out). In the control group, the rehabilitation exercise combined with routine acupuncture therapy was used, and in the trial group, on the base of the treatment as the control group, the elongated needling at the points of hand and foot yang meridians and the Governor Vessel was supplemented. In the two groups, the treatment was given once daily, and 1 course of treatment was composed of 14 days, a total of 6 courses were required in the trial. Separately, before treatment, and 1, 2 and 3 months after treatment, between two groups, the score of visual analogue scale (VAS) and that of Berg balance scale (BBS), as well as muscle strength were compared；the neural function was evaluated using the national institutes of health stroke scale (NIHSS) and the serum contents of nitricoxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA in the patients. RESULTS: Compared with those before treatment, VAS score and NIHSS score were all decreased (P<0.05) in the trial and the control group after 1 month, 2 months and 3 months of treatment, and BBS score was increased (P<0.05)；and the case proportion of muscle strength grade 4 and 5 was higher (P<0.05) in the trial group. In the control group, the proportion of grade 4 increased after treatment for 2 months (P<0.05), and that of grade 4 and 5 increased after treatment for 3 months (P<0.05). The serum contents of NOS and SOD were increased (P<0.05), and MDA was decreased (P<0.05) after 3 months of treatment in the two groups. In comparison with the control group at the same time point, VAS score and NIHSS score were lower (P<0.05), BBS score higher (P<0.05) and the muscle strength grade was improved (P<0.05, P<0.01) after 1, 2 and 3 months of treatment, respectively；and the serum contents of NOS and SOD increased (P<0.05), and MDA decreased (P<0.05) after 3 months of treatment in the trial group. CONCLUSIONS: The elongated needling at the points of hand and foot yang meridians and the Governor Vessel, combined with the routine acupuncture therapy alleviates CPSP, improves balance and muscle strength and promotes the recovery of neural function in the patients with post-stroke hemiplegia, the mechanism may be related to antioxidant damage.

Individual-finger motor imagery classification: a data-driven approach with Shapley-informed augmentation.

Objective. Classifying motor imagery (MI) tasks that involve fine motor control of the individual five fingers presents unique challenges when utilizing electroencephalography (EEG) data. In this paper, we systematically assess the classification of MI functions for the individual five fingers using single-trial time-domain EEG signals. This assessment encompasses both within-subject and cross-subject scenarios, supported by data-driven analysis that provides statistical validation of the neural correlate that could potentially discriminate between the five fingers.Approach. We present Shapley-informed augmentation, an informed approach to enhance within-subject classification accuracy. This method is rooted in insights gained from our data-driven analysis, which revealed inconsistent temporal features encoding the five fingers MI across sessions of the same subject. To evaluate its impact, we compare within-subject classification performance both before and after implementing this augmentation technique.Main results. Both the data-driven approach and the model explainability analysis revealed that the parietal cortex contains neural information that helps discriminate the individual five fingers' MI apart. Shapley-informed augmentation successfully improved classification accuracy in sessions severely affected by inconsistent temporal features. The accuracy for sessions impacted by inconsistency in their temporal features increased by an average of26.3%±6.70, thereby enabling a broader range of subjects to benefit from brain-computer interaction (BCI) applications involving five-fingers MI classification. Conversely, non-impacted sessions experienced only a negligible average accuracy decrease of2.01±5.44%. The average classification accuracy achieved is around 60.0% (within-session), 50.0% (within-subject) and 40.0% (leave-one-subject-out).Significance. This research offers data-driven evidence of neural correlates that could discriminate between the individual five fingers MI and introduces a novel Shapley-informed augmentation method to address temporal variability of features, ultimately contributing to the development of personalized systems.

Effect of photobiomodulation therapy on pain perception during anesthetic puncture of dental local anesthesia: A systematic review.

BACKGROUND: Local anesthetic puncture is often related to the experience of pain. This study aimed to systematically analyze the literature on changes in pain perception during the anesthetic puncture of dental local anesthesia after Photobiomodulation Therapy (PBMT). MATERIAL AND METHODS: An electronic search was performed in eight primary databases (Embase, LILACS, BBO, LIVIVO, MedLine via PubMed, SciELO, Scopus, and Web of Science) and three additional ones (EASY, Google Scholar, and OATD) to partially capture the "gray literature". The PICO strategy was used to identify randomized clinical trials evaluating the analgesic effect of PBMT in the anesthetic puncture site of dental local anesthesia compared to placebo or control groups, without restrictions on publication language and year. Two reviewers extracted the data and assessed the individual risk of bias of the eligible studies using the Cochrane Collaboration Risk of Bias Tool version 2.0. RESULTS: The electronic search found 3,485 records, of which eight met the eligibility criteria and were included in the qualitative synthesis. The studies were published from 2011 to 2022. None of the included studies had a low risk of bias. PBMT groups showed no significant difference in pain scores compared to placebo and control groups of most studies. CONCLUSION: Based on a low to very low certainty of evidence, PBMT seems to have no effect on pain perception during anesthetic puncture in patients undergoing dental local anesthesia.