Application of TCM Nursing in Post-anesthesia Recovery Room Under Integrated Management Mode.

Objective: To explore the effect of traditional Chinese medicine (TCM) nursing under the integrated management mode during anesthesia recovery. Methods: The researchers' hospital admitted 114 patients who underwent general anesthesia between August 2022 and April 2023. Based on the admission order, these patients were divided into a control group (N=57) and an observation group (N=57). The control group received routine nursing intervention, while the observation group received comprehensive TCM nursing management, which included therapies such as cupping, acupressure, massage, herbal decoction, and mirabilite application. The study evaluated the psychological status, recovery indexes after anesthesia, comfort level, incidence of complications, and patient satisfaction with nursing care. Results: Compared to the control group, the observation group showed significant improvement in their psychological well-being (P < .05) and better recovery outcomes after anesthesia (P < .05). Additionally, the observation group reported higher levels of comfort (P < .05), a lower incidence of complications (8.77% vs 29.82%, P < .05), and greater satisfaction with nursing care (98.25% vs 84.21%, P < .05) compared to the control group. Conclusion: Integrated management of traditional Chinese medicine effectively reduces postoperative adverse events, improves treatment outcomes, and facilitates patient recovery. Its benefits are evident, and its feasibility is well-established.

The role of hypertension in the relationship between leisure screen time, physical activity and migraine: a 2-sample Mendelian randomization study.

BACKGROUND: The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality. METHODS: Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set. Estimates derived from the two datasets were combined using fixed-effects meta-analysis. Two-step univariable MR (UVMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to evaluate 19 potential mediators of association and determine the proportions of these mediators. RESULTS: The combined effect of inverse variance weighted revealed that a one standard deviation (SD) increase in genetically predicted Leisure screen time (LST) was associated with a 27.7% increase (95% CI: 1.14-1.44) in migraine risk, while Moderate or/and vigorous physical activity (MVPA) was associated with a 26.9% decrease (95% CI: 0.61-0.87) in migraine risk. The results of the mediation analysis indicated that out of the 19 modifiable metabolic risk factors examined, hypertension explains 24.81% of the relationship between LST and the risk of experiencing migraine. Furthermore, hypertension and diastolic blood pressure (DBP) partially weaken the association between MVPA and migraines, mediating 4.86% and 4.66% respectively. CONCLUSION: Our research findings indicated that both LST and MVPA in lifestyle have independent causal effects on migraine. Additionally, we have identified that hypertension and DBP play a mediating role in the causal pathway between these two factors and migraine.

Inhibiting PAC1 receptor internalization and endosomal ERK pathway activation may ameliorate hyperalgesia in a chronic migraine rat model.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide widely distributed in the trigeminovascular system (TVS) and higher brain regions. At present, the underlying mechanism of PACAP/PACAP type1 (PAC1) receptor in migraine generation remains unclear. METHODS: The rat model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and hot plate tests were used to measure the mechanical and thermal thresholds. The expression levels of c-Fos, calcitonin gene-related peptide (CGRP), PACAP, PAC1, protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (ERK) were assessed by western blotting or immunofluorescence staining. The internalization of PAC1 receptor was visualized by fluorescence microscope and laser scanning confocal microscope. RESULTS: The results showed that c-Fos and CGRP expression significantly increased after repeated administrations of NTG or PACAP. Pitstop2 notably improved hyperalgesia in CM rats, while PACAP6-38 offered no benefit. In addition, PACAP-induced PAC1 receptor internalization, PKA and ERK pathways activation were blocked by Pitstop2 instead of PACAP6-38. CONCLUSIONS: Our results demonstrate that inhibition of PAC1 receptor internalization could effectively improve allodynia in CM rats by restraining ERK signaling pathway activation in a chronic migraine rat model. Modulation of receptor internalization may be a novel perspective to explore specific mechanisms of PACAP signaling activation in the trigeminal vascular system.

Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.

OBJECTIVE: To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine. BACKGROUND: Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. METHODS: A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)-like rats were quantified and the changes in Treg/Th17-related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2-(1'-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and AHR antagonist CH-223191 on pain behavior, c-Fos, calcitonin gene-related peptide (CGRP), AHR, and Treg/Th17-related factor expression in CM-like rats. RESULTS: Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c-Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor-related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta-1 was decreased, while that of interleukin (IL)-10 and IL-22 was increased in the TNC. The AHR agonist ITE alleviated migraine-like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17-related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH-223191 did not alleviate migraine-like pain behaviors in rats; and even exacerbated them. CONCLUSIONS: The AHR participates in the development of CM by regulating Treg/Th17-related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment.

PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.

AIMS: Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model. METHODS: Sprague-Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons. RESULTS: The results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38. CONCLUSIONS: Our results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.

SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1α positive feedback loop.

Migraine is the second highest cause of disability worldwide, bringing a huge socioeconomic burden. Improving mitochondrial function has promise as an effective treatment strategy for migraine. Szeto-Schiller peptide (SS-31) is a new mitochondria-targeted tetrapeptide molecule that has been shown to suppress the progression of diseases by restoring mitochondrial function, including renal disease, cardiac disease, and neurodegenerative disease. However, whether SS-31 has a therapeutic effect on migraine remains unclear. The aim of this study is to clarify the treatment of SS-31 for headache and its potential mechanisms. Here we used a mouse model induced by repeated dural infusion of inflammatory soup (IS), and examined roles of Sirt3/Pgc-1α positive feedback loop in headache pathogenesis and mitochondrial function. Our results showed that repeated IS infusion impaired mitochondrial function, mitochondrial ultrastructure and mitochondrial homeostasis in the trigeminal nucleus caudalis (TNC). These IS-induced damages in TNC were reversed by SS-31. In addition, IS-induced nociceptive responses were simultaneously alleviated. The effects of SS-31 on mitochondrial function and mitochondrial homeostasis (mainly mitochondrial biogenesis) were attenuated partially by the inhibitor of Sirt3/Pgc-1α. Overexpression of Sirt3/Pgc-1α increased the protein level of each other. These results indicated that SS-31 alleviated nociceptive responses and restored mitochondrial function in an IS-induced headache mouse model via Sirt3/Pgc-1α positive feedback loop. SS-31 has the potential to be an effective drug candidate for headache treatment.

Clinical study on effect of wrist-ankle acupuncture on incidence of hypertension after intubation during induction of general anesthesia.

OBJECTIVE: To observe the effect of wrist-ankle acupuncture on the incidence of hypertension after tracheal intubation during induction of general anesthesia. METHODS: 200 patients receiving selective surgery under tracheal intubation and general anesthesia in our Hospital were selected and divided into control group and wrist-ankle acupuncture group using the random number table method, with 100 patients in each group. Sufentanil, cisatracurium besilate, remifentanil, etomidate and lidocaine hydrochloride were used for anesthesia induction, and intravenously injected according to the onset time of drugs, successively. The wrist-ankle acupuncture group was needled in bilateral upper 1, 2 and 3 areas, while the control group was treated with false acupuncture.Blood pressure and related blood biochemical indexes were measured and observed at different stages in each group. RESULT: The incidence of blood pressure exceeding 20% and 30% of basal blood pressure within 5 minutes after intubation was as follows:wrist-ankle acupuncture group 11.83% and 6.45%; control group 29.79% and 22.34%, The incidence in the study group was lower than that in the control group. Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that before induction (P < .05), and plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). The plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). CONCLUSION: wrist-ankle acupuncture can prevent hypertension after intubation during anesthesia induction. Moreover, it is safe, effective, minimally invasive. Therefore, it is easy to be popularized in clinical practice.

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats.

BACKGROUND: The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine. METHODS: Model rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation. RESULTS: Microglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia. CONCLUSIONS: Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.

Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1ß and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine.

An effective feature extraction method based on GDS for atrial fibrillation detection.

Atrial fibrillation (AF) is a common and extremely harmful arrhythmia disease. Automatic detection of AF based on ECG helps accurate and timely detection of the condition. However, the existing AF detection methods are mostly based on complex signal transformation or precise waveform localization. This is a big challenge for complex, variable, and susceptible ECG signals. Therefore, we propose a simple feature extraction method based on gradient set (GDS) for AF detection. The method first calculates the GDS of the ECG segment and then calculates the statistical distribution feature and the information quantity feature of the GDS as the input of the classifier. Experiments on four databases include 146 subjects show that the feature extraction method for detecting AF proposed in this paper has the characteristics of simple calculation, noise tolerance, and high adaptability to all kinds of classifiers, and got the best performance on the DNN classifier we designed. Therefore, it is a good choice for feature extraction in AF detection.

Unlocking the relationships among population structure, plant architecture, growing season, and environmental adaptation in Henan wheat cultivars.

BACKGROUND: Ecological environments shape plant architecture and alter the growing season, which provides the basis for wheat genetic improvement. Therefore, understanding the genetic basis of grain yield and yield-related traits in specific ecological environments is important. RESULTS: A structured panel of 96 elite wheat cultivars grown in the High-yield zone of Henan province in China was genotyped using an Illumina iSelect 90 K SNP assay. Selection pressure derived from ecological environments of mountain front and plain region provided the initial impetus for population divergence. This determined the dominant traits in two subpopulations (spike number and spike percentage were dominance in subpopulation 2:1; thousand-kernel weight, grain filling rate (GFR), maturity date (MD), and fertility period (FP) were dominance in subpopulation 2:2), which was also consistent with their inheritance from the donor parents. Genome wide association studies identified 107 significant SNPs for 12 yield-related traits and 10 regions were pleiotropic to multiple traits. Especially, GY was co-located with MD/FP, GFR and HD at QTL-ple5A, QTL-ple7A.1 and QTL-ple7B.1 region. Further selective sweep analysis revealled that regions under selection were around QTLs for these traits. Especially, grain yield (GY) is positively correlated with MD/FP and they were co-located at the VRN-1A locus. Besides, a selective sweep signal was detected at VRN-1B locus which was only significance to MD/FP. CONCLUSIONS: The results indicated that extensive differential in allele frequency driven by ecological selection has shaped plant architecture and growing season during yield improvement. The QTLs for yield and yield components detected in this study probably be selectively applied in molecular breeding.

Molecular characterization of a novel TaGL3-5A allele and its association with grain length in wheat (Triticum aestivum L.).

KEY MESSAGE: We isolated a novel allele associated with grain length and grain weight in wheat, TaGL3-5A-G. The TaGL3-5A-G allele frequency is low in wheat, so it has potential for breeding. Selection of large-grain wheat showing big grain sink potential and strong sink activity is becoming an important objective in breeding programs. Here, we cloned a wheat TaGL3-5A gene that was orthologous to rice GL3 and was phylogenetically clustered with both monocot PPKL1 and its expression pattern was similar to grain size change at early and middle stages of seed development. The isolated TaGL3-5A genomic sequence was 10,227 bp long and included 21 exons and 20 introns. Alignment of the TaGL3-5A sequences in Beinong 6 and Yanda 1817 showed a G/A substitution in the 11th exon (position 5946) that would lead to an amino acid change (Met/Ile). Subsequently, a KASP marker was designed based on this SNP. Genotyping of RILs showed that TaGL3-5A was located on the wheat 5AL chromosome and was colocated with a significant grain length QTL in three independent environments and mean value. Association analysis revealed that the TaGL3-5A-G allele was significantly correlated with longer grains and higher thousand-kernel weight. Haplotype association analysis indicated that TaGL3-5A-G could enhance grain traits in combination with TaGS5-3A and TaGW2-6B. The frequency of TaGL3-5A-G was higher in modern cultivars than in landraces but was still low in major Chinese wheat production areas. Additionally, the frequency of the TaGL3-5A-G allele in hexaploid wheat was slightly lower than in Triticum dicoccoides and much lower than in Triticum turgidum. Hence, T. dicoccoides and T. turgidum represent valuable resources for transferring the TaGL3-5A-G allele into common wheat, which should lead to longer grain length.

Cloning, characterization of TaGS3 and identification of allelic variation associated with kernel traits in wheat (Triticum aestivum L.).

BACKGROUND: Grain weight is an important yield component. Selection of advanced lines with heavy grains show high grain sink potentials and strong sink activity, which is an increasingly important objective in wheat breeding programs. Rice OsGS3 has been identified as a major quantitative trait locus for both grain weight and grain size. However, allelic variation of GS3 has not been characterized previously in hexaploid wheat. RESULTS: We cloned 2445, 2393, and 2409 bp sequences of the homologs TaGS3-4A, TaGS3-7A, and TaGS3-7D in wheat 'Changzhi 6406', a cultivar that shows high grain weight. The TaGS3 genes each contained five exons and four introns, and encoded a deduced protein of 170, 169, and 169 amino acids, respectively. Phylogenetic analysis of plant GS3 protein sequences revealed GS3 to be a monocotyledon-specific gene and the GS3 proteins were resolved into three classes. The length of the atypical Gγ domain and the cysteine-rich region was conserved within each class and not conserved between classes. A single-nucleotide polymorphism in the fifth exon (at position 1907) of TaGS3-7A leads to an amino acid change (ALA/THR) and showed different frequencies in two pools of Chinese wheat accessions representing extremes in grain weight. Association analysis indicated that the TaGS3-7A-A allele was associated with higher grain weight in the natural population. The TaGS3-7A-A allele was favoured in global modern wheat cultivars but the allelic frequency varied among different wheat-production regions of China, which indicated that this allele is of potential utility to improve wheat grain weight in certain wheat-production areas of China. CONCLUSIONS: The novel molecular information on wheat GS3 homologs and the KASP functional marker designed in this study may be useful in marker-assisted breeding for genetic improvement of wheat.

Alternative splicing results in a lack of starch synthase IIa-D in Chinese wheat landrace.

We evaluated the SGP-1 protein composition of 368 Chinese wheat landraces using SDS-PAGE. The SGP-D1 null type was identified in three accessions (Xiaoqingmang, Pushanbamai, and P119). An 18-bp deletion and 9-bp variation were found at the junction region of the 7th intron and 8th exon, leading to deletion of the intron-exon junction recognition site AG when aligned the 8261-bp DNA sequence of TaSSIIa-D in Pushanbamai with that of Chinese Spring. Four cDNA types with mis-spliced isoforms were subsequently detected through amplification of TaSSIIa-D cDNAs. Among these, nine type II cDNAs with a 16-bp deletion in the 8th exon were detected, indicating that the major transcriptional pattern of TaSSIIa in Pushanbamai is type II. In the type IV cDNA, a 97-bp sequence remains undeleted in the end of the 5th exon. The amylose content in Pushanbamai was significantly higher than that in all control lines under field conditions, which suggested that deletion of SGP-D1 has an efficient impact on amylose content. As the TaSSIIa gene plays an important role in regulating the content of amylose, it is anticipated that these natural variants of TaSSIIa-D will provide useful resources for quality improvement in wheat.

Desired properties of polymeric hydrogel vitreous substitute.

Vitreous replacement is a commonly employed method for treating a range of ocular diseases, including posterior vitreous detachment, complex retinal detachment, diabetic retinopathy, macular hole, and ocular trauma. Various clinical substitutes for vitreous include air, expandable gas, silicone oil, heavy silicone oil, and balanced salt solution. However, these substitutes have drawbacks such as short retention time, cytotoxicity, high intraocular pressure, and the formation of cataracts, rendering them unsuitable for long-term treatment. Polymeric hydrogels possess the potential to serve as ideal vitreous substitutes due to their structure-mimicking to natural vitreous and adjustable mechanical properties. Replacement with hydrogels as the tamponade can help maintain the shape of the eyeball, apply pressure to the detached retina, and ensure the metabolic transport of substances without impairing vision. This literature review examines the required properties of artificial vitreous, including the optical properties, rheological properties, expansive force action, and physiological and biochemical functions of chemically and physically crosslinked hydrogels. The strategies for enhancing the biocompatibility and injectability of hydrogels are also summarized and discussed. From a clinical ophthalmology perspective, this paper presents the latest developments in vitreous replacement, providing clinicians with a comprehensive understanding of hydrogel clinical applications, which offers guidance for future design directions and methodologies for hydrogel development.

A new experimental rat model of nocebo-related nausea involving double mechanisms of observational learning and conditioning.

AIM: The nocebo effect, such as nausea and vomiting, is one of the major reasons patients discontinue therapy. The underlying mechanisms remain unknown due to a lack of reliable experimental models. The goal of this study was to develop a new animal model of nocebo-related nausea by combining observational learning and Pavlovian conditioning paradigms. METHODS: Male Sprague-Dawley rats with nitroglycerin-induced migraine were given 0.9% saline (a placebo) or LiCl (a nausea inducer) following headache relief, according to different paradigms. RESULTS: Both strategies provoked nocebo nausea responses, with the conditioning paradigm having a greater induction impact. The superposition of two mechanisms led to a further increase in nausea responses. A preliminary investigation of the underlying mechanism revealed clearly raised peripheral and central cholecystokinin (CCK) levels, as well as specific changes in the 5-hydroxytryptamine and cannabinoid systems. Brain networks related to emotion, cognition, and visceral sense expressed higher c-Fos-positive neurons, including the anterior cingulate cortex (ACC), insula, basolateral amygdala (BLA), thalamic paraventricular nucleus (PVT), hypothalamic paraventricular nucleus (PVN), nucleus tractus solitarius (NTS), periaqueductal gray (PAG), and dorsal raphe nucleus-dorsal part (DRD). We also found that nausea expectances in the model could last for at least 12 days. CONCLUSION: The present study provides a useful experimental model of nocebo nausea that might be used to develop potential molecular pathways and therapeutic strategies for nocebo.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial.

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64-1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic ß cells.

Pancreatic ß cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as ß cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in ß cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in ß cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in ß cells.

RemixFormer++: A Multi-modal Transformer Model for Precision Skin Tumor Differential Diagnosis with Memory-efficient Attention.

Diagnosing malignant skin tumors accurately at an early stage can be challenging due to ambiguous and even confusing visual characteristics displayed by various categories of skin tumors. To improve diagnosis precision, all available clinical data from multiple sources, particularly clinical images, dermoscopy images, and medical history, could be considered. Aligning with clinical practice, we propose a novel Transformer model, named Remix-Former++ that consists of a clinical image branch, a dermoscopy image branch, and a metadata branch. Given the unique characteristics inherent in clinical and dermoscopy images, specialized attention strategies are adopted for each type. Clinical images are processed through a top-down architecture, capturing both localized lesion details and global contextual information. Conversely, dermoscopy images undergo a bottom-up processing with two-level hierarchical encoders, designed to pinpoint fine-grained structural and textural features. A dedicated metadata branch seamlessly integrates non-visual information by encoding relevant patient data. Fusing features from three branches substantially boosts disease classification accuracy. RemixFormer++ demonstrates exceptional performance on four single-modality datasets (PAD-UFES-20, ISIC 2017/2018/2019). Compared with the previous best method using a public multi-modal Derm7pt dataset, we achieved an absolute 5.3% increase in averaged F1 and 1.2% in accuracy for the classification of five skin tumors. Furthermore, using a large-scale in-house dataset of 10,351 patients with the twelve most common skin tumors, our method obtained an overall classification accuracy of 92.6%. These promising results, on par or better with the performance of 191 dermatologists through a comprehensive reader study, evidently imply the potential clinical usability of our method.

Adversarial Spatiotemporal Contrastive Learning for Electrocardiogram Signals.

Extracting invariant representations in unlabeled electrocardiogram (ECG) signals is a challenge for deep neural networks (DNNs). Contrastive learning is a promising method for unsupervised learning. However, it should improve its robustness to noise and learn the spatiotemporal and semantic representations of categories, just like cardiologists. This article proposes a patient-level adversarial spatiotemporal contrastive learning (ASTCL) framework, which includes ECG augmentations, an adversarial module, and a spatiotemporal contrastive module. Based on the ECG noise attributes, two distinct but effective ECG augmentations, ECG noise enhancement, and ECG noise denoising, are introduced. These methods are beneficial for ASTCL to enhance the robustness of the DNN to noise. This article proposes a self-supervised task to increase the antiperturbation ability. This task is represented as a game between the discriminator and encoder in the adversarial module, which pulls the extracted representations into the shared distribution between the positive pairs to discard the perturbation representations and learn the invariant representations. The spatiotemporal contrastive module combines spatiotemporal prediction and patient discrimination to learn the spatiotemporal and semantic representations of categories. To learn category representations effectively, this article only uses patient-level positive pairs and alternately uses the predictor and the stop-gradient to avoid model collapse. To verify the effectiveness of the proposed method, various groups of experiments are conducted on four ECG benchmark datasets and one clinical dataset compared with the state-of-the-art methods. Experimental results showed that the proposed method outperforms the state-of-the-art methods.