AIGO-DTI: Predicting Drug-Target Interactions Based on Improved Drug Properties Combined with Adaptive Iterative Algorithms.

Artificial intelligence-based methods for predicting drug-target interactions (DTIs) aim to explore reliable drug candidate targets rapidly and cost-effectively to accelerate the drug development process. However, current methods are often limited by the topological regularities of drug molecules, making them difficult to generalize to a broader chemical space. Additionally, the use of similarity to measure DTI network links often introduces noise, leading to false DTI relationships and affecting the prediction accuracy. To address these issues, this study proposes an Adaptive Iterative Graph Optimization (AIGO)-DTI prediction framework. This framework integrates atomic cluster information and enhances molecular features through the design of functional group prompts and graph encoders, optimizing the construction of DTI association networks. Furthermore, the optimization of graph structure is transformed into a node similarity learning problem, utilizing multihead similarity metric functions to iteratively update the network structure to improve the quality of DTI information. Experimental results demonstrate the outstanding performance of AIGO-DTI on multiple public data sets and label reversal data sets. Case studies, molecular docking, and existing research validate its effectiveness and reliability. Overall, the method proposed in this study can construct comprehensive and reliable DTI association network information, providing new graphing and optimization strategies for DTI prediction, which contribute to efficient drug development and reduce target discovery costs.

Six new diterpenoids with anti-inflammatory and cytotoxic activity from Isodon serra.

Diterpenoids occupy an important slot of the natural products diversity space with wide ranges of bioactivities and complex structures, providing potential applications for the development of therapeutics. In this study, we reported four new abietane-type diterpenoids viroxocin B-E (1-4), a new totarane-type diterpenoid viroxocin F (5), and a new sempervirane-type diterpenoid viroxocin G (6) along with four known compounds (7-10), isolated and identified from a widely used Traditional Chinese Medicine, Isodon serra (I. serra). Their structures were established by spectroscopic data analysis, experimental and calculated electronic circular dichroism (ECD) data, as well as X-ray diffraction analysis. Compounds 2, 5, 7, 8 and 10 exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 60% at 10 µM. Compound 7 showed cytotoxicity against human renal cell carcinoma 769P at 20 µM, the inhibition rate was 52.66%.

Etiological diagnostic performance of probe capture-based targeted next-generation sequencing in bloodstream infection.

Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI. Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China. All 80 participants underwent simultaneous blood culture, blood mNGS, and blood tNGS after admission when febrile, and the results were compared. Results: Among the 80 participants, 11 were clinically diagnosed with noninfectious fever, and 69 were diagnosed with BSI. Blood tNGS had a higher sensitivity for the diagnosis of BSI than blood culture (91.3% vs. 23.2%, P<0.001) and blood mNGS (91.3% vs. 69.6%, P=0.001). There was no significant difference in specificity between blood mNGS and tNGS (81.8% vs. 100.0%, P=0.13). Blood tNGS demonstrated a faster turnaround time than blood culture and blood mNGS. In 22 (31.9%) patients with BSI, targeted adjustment of the anti-infectious therapy according to the blood tNGS results resulted in clinical improvement. Conclusions: Blood tNGS may be a promising tool for detecting potential pathogens in patients with BSI. The application of blood tNGS for BSI could guide anti-infectious treatment strategies and might improve clinical outcomes.

An improved differential evolution algorithm for multi-modal multi-objective optimization.

Multi-modal multi-objective problems (MMOPs) have gained much attention during the last decade. These problems have two or more global or local Pareto optimal sets (PSs), some of which map to the same Pareto front (PF). This article presents a new affinity propagation clustering (APC) method based on the Multi-modal multi-objective differential evolution (MMODE) algorithm, called MMODE_AP, for the suit of CEC'2020 benchmark functions. First, two adaptive mutation strategies are adopted to balance exploration and exploitation and improve the diversity in the evolution process. Then, the affinity propagation clustering method is adopted to define the crowding degree in decision space (DS) and objective space (OS). Meanwhile, the non-dominated sorting scheme incorporates a particular crowding distance to truncate the population during the environmental selection process, which can obtain well-distributed solutions in both DS and OS. Moreover, the local PF membership of the solution is defined, and a predefined parameter is introduced to maintain of the local PSs and solutions around the global PS. Finally, the proposed algorithm is implemented on the suit of CEC'2020 benchmark functions for comparison with some MMODE algorithms. According to the experimental study results, the proposed MMODE_AP algorithm has about 20 better performance results on benchmark functions compared to its competitors in terms of reciprocal of Pareto sets proximity (rPSP), inverted generational distances (IGD) in the decision (IGDX) and objective (IGDF). The proposed algorithm can efficiently achieve the two goals, i.e., the convergence to the true local and global Pareto fronts along with better distributed Pareto solutions on the Pareto fronts.

High spatial resolution elevation change dataset derived from ICESat-2 crossover points on the Tibetan Plateau.

Understanding elevation changes on the Tibetan Plateau is crucial to comprehend the changes in topography, landscape, climate, environmental conditions, and water resources. However, some of the current products that track elevation changes only cover specific surface types or limited areas, and others have low spatial resolution. We propose an algorithm to extract ICESat-2 crossover points dataset for the Tibetan Plateau, and form a dataset. The crossover points dataset has a density of 2.015 groups/km², and each group of crossover points indicates the amount of change in elevation before and after a period of time over an area of approximately 17 meters in diameter. Comparing ICESat-2 crossover points data with existing studies on glaciers and lakes, we demonstrated the reliability of the derived elevation changes. The ICESat-2 crossover points provide a refined data source for understanding high-spatial-resolution elevation changes on the Tibetan Plateau. This dataset can provide validation data for various studies that require high-precision or high-resolution elevation change data on the Tibetan Plateau.

Pinning-Based Neural Control for Multiagent Systems With Self-Regulation Intermediate Event-Triggered Method.

A pinning-based self-regulation intermediate event-triggered (ET) funnel tracking control strategy is proposed for uncertain nonlinear multiagent systems (MASs). Based on the backstepping framework, a pinning control strategy is designed to achieve the tracking control objective, which only uses the communication weight between the agents without additional feedback parameters. Moreover, by designing a self-regulation triggered condition based on the tracking error, the intermediate triggered signal is calculated to replace the continuous signal in the controller, so as to achieve the goal of discontinuous update of the controller signal, and this mechanism does not need to add additional compensation function to the controller signal. At the same time, the funnel method is adopted to restrict the error of step n and avoid the possible negative impact caused by control signal. Furthermore, the nonlinear noncontinuous faults are compensated by the disturbance observer. Then, the Lyapunov stability theorem is used to prove that all signals of the closed-loop system are semiglobally uniformly ultimately bounded (SGUUB). Finally, some simulation results confirm the effectiveness of the proposed control scheme.

H2O-Mg2+ Waltz-Like Shuttle Enables High-Capacity and Ultralong-Life Magnesium-Ion Batteries.

Mg-ion batteries (MIBs) are promising next-generation secondary batteries, but suffer from sluggish Mg2+ migration kinetics and structural collapse of the cathode materials. Here, an H2O-Mg2+ waltz-like shuttle mechanism in the lamellar cathode, which is realized by the coordination, adaptive rotation and flipping, and co-migration of lattice H2O molecules with inserted Mg2+, leading to the fast Mg2+ migration kinetics, is reported; after Mg2+ extraction, the lattice H2O molecules rearrange to stabilize the lamellar structure, eliminating structural collapse of the cathode. Consequently, the demo cathode of Mg0.75V10O24·nH2O (MVOH) exhibits a high capacity of 350 mAh g-1 at a current density of 50 mA g-1 and maintains a capacity of 70 mAh g-1 at 4 A g-1. The full aqueous MIB based on MVOH delivers an ultralong lifespan of 5000 cycles The reported waltz-like shuttle mechanism of lattice H2O provides a novel strategy to develop high-performance cathodes for MIBs as well as other multivalent-ion batteries.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

Dual-Defect Engineering Strategy Enables High-Durability Rechargeable Magnesium-Metal Batteries.

Rechargeable magnesium-metal batteries (RMMBs) are promising next-generation secondary batteries; however, their development is inhibited by the low capacity and short cycle lifespan of cathodes. Although various strategies have been devised to enhance the Mg2+ migration kinetics and structural stability of cathodes, they fail to improve electronic conductivity, rendering the cathodes incompatible with magnesium-metal anodes. Herein, we propose a dual-defect engineering strategy, namely, the incorporation of Mg2+ pre-intercalation defect (P-Mgd) and oxygen defect (Od), to simultaneously improve the Mg2+ migration kinetics, structural stability, and electronic conductivity of the cathodes of RMMBs. Using lamellar V2O5·nH2O as a demo cathode material, we prepare a cathode comprising Mg0.07V2O5·1.4H2O nanobelts composited with reduced graphene oxide (MVOH/rGO) with P-Mgd and Od. The Od enlarges interlayer spacing, accelerates Mg2+ migration kinetics, and prevents structural collapse, while the P-Mgd stabilizes the lamellar structure and increases electronic conductivity. Consequently, the MVOH/rGO cathode exhibits a high capacity of 197 mAh g-1, and the developed Mg foil//MVOH/rGO full cell demonstrates an incredible lifespan of 850 cycles at 0.1 A g-1, capable of powering a light-emitting diode. The proposed dual-defect engineering strategy provides new insights into developing high-durability, high-capacity cathodes, advancing the practical application of RMMBs, and other new secondary batteries.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

Enhancement of antitumor response of staphylococcal enterotoxin C2 mutant 2M-118 by promoting cell-mediated antitumor immunity.

BACKGROUND: Staphylococcal enterotoxin C2 (SEC2) is used as an immunotherapeutic drug in China. However, SEC2 are limited due to its immunosuppressive and toxic effects. A SEC2 2M-118 (H118A/T20L/G22E) mutant generated by site-directed mutagenesis was studied to elucidate the underlying antitumor mechanism. METHODS: The effects of 2M-118 on mouse fibrosarcoma (Meth-A) cells and cytokine responses were tested in vitro using a transwell assay and ELISA, respectively. 2M-118 effect on immune function in tumor-bearing mice was tested. Cytokine levels and antitumor responses were measured using ELISA and flow cytometry, respectively. TUNEL staining and immunohistochemistry were employed to detect the tumor apoptosis and CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor tissue. RESULTS: 2M-118 demonstrated the growth inhibition on tumor cells, increase of cytokines production (IL-2, IFN-γ, and TNF-α) and splenocyte proliferation in vitro. 2M-118 effectively inhibited tumor development and increased lymphocytes and cytokines in a tumor-bearing mouse model. Additionally, 2M-118 regulated the tumormicroenvironment by reducing the number of myeloid-derived suppressor cells (MDSCs), increasing the number of TILs, and inducing tumorcell apoptosis. CONCLUSION: 2M-118 promotes immune function and enhances antitumor response. This indicates that 2M-118 could potentially be developed as a novel anti-tumor drug with-highefficiencyandlowtoxicity.

Cloning, expression and application of a novel laccase derived from water buffalo ruminal lignin-degrading bacteria.

Water buffalo is the only mammal found to degrade lignin so far, and laccase plays an indispensable role in the degradation of lignin. In this study, multiple laccase genes were amplified based on the water buffalo rumen derived lignin-degrading bacteria Bacillus cereus and Ochrobactrum pseudintermedium. Subsequently, the corresponding recombinant plasmids were transformed into E. coli expression system BL21 (DE3) for induced expression by Isopropyl-ß-D-thiogalactopyranoside (IPTG). After preliminary screening, protein purification and enzyme activity assays, Lac3833 with soluble expression and high enzyme activity was selected to test its characteristics, especially the ability of lignin degradation. The results showed that the optimum reaction temperature of Lac3833 was 40 °C for different substrates. The relative activity of Lac3833 reached the highest at pH 4.5 and pH 5.5 when the substrates were ABTS or 2,6-DMP and guaiacol, respectively. Additionally, Lac3833 could maintain high enzyme activity in different temperatures, pH and solutions containing Na+, K+, Mg2+, Ca2+ and Mn2+. Importantly, compared to negative treatment, recombinant laccase Lac3833 treatment showed that it had a significant function in degrading lignin. In conclusion, this is a pioneering study to produce recombinant laccase with lignin-degrading ability by bacteria from water buffalo rumen, which will provide new insights for the exploitation of more lignin-degrading enzymes.

Switched Control of HyTAQs: A Framework of Stochastic Hybrid Fuzzy Systems With Variable Dimensions.

This article is concerned with the switched control of hybrid terrestrial and aerial quadrotors (HyTAQs) via stochastic hybrid fuzzy system methodology, in which the terrestrial and aerial mode switching is subject to a Markov process with lower-bounded sojourn time. For the first time, the bimodal nonlinear attitude dynamics of HyTAQs is analyzed and modeled based on the Takagi-Sugeno (T-S) fuzzy model, and switched fuzzy controllers are developed to stabilize the hybrid fuzzy system. The characteristic of state dimension switching caused by ground contact is modeled via the singular system presentation with mode-dependent singularity matrices, based on which numerically testable criteria of stability and stabilization in the stochastic sense are derived. Compared with the previous control approaches based on Markov jump systems, the proposed one is able to describe the deterministic dwelling duration in practice and integrate multiple subsystems with algebraic equations of different dimensions, while achieving lower conservatism. Illustrative examples are provided to demonstrate the effectiveness and potential of the designed variable-dimension fuzzy controllers.

Spatial Heterogeneity of b Values in Northeastern Tibetan Plateau and Its Interpretation.

The northeastern margin of the Tibetan Plateau (NE Tibetan Plateau) exhibits active geological structures and has experienced multiple strong earthquakes, with M ≥ 7, throughout history. Particularly noteworthy is the 1920 M81/2 earthquake in the Haiyuan region that occurred a century ago and is documented as one of the deadliest earthquakes. Consequently, analyzing seismic risks in the northeastern margin of the Tibetan Plateau holds significant importance. The b value, a crucial parameter for seismic activity, plays a pivotal role in seismic hazard analyses. This study calculates the spatial b values in this region based on earthquake catalogs since 1970. The study area encompasses several major active faults, and due to variations in b values across different fault types, traditional grid-search methods may introduce significant errors in calculating the spatial b value within complex fault systems. To address this, we employed the hierarchical space-time point-process (HIST-PPM) method proposed by Ogata. This method avoids partitioning earthquake samples, optimizes parameters using Akaike's Bayesian Information Criterion (ABIC) with entropy maximization, and theoretically allows for a higher spatial resolution and more accurate b value calculations. The results indicate a high spatial heterogeneity in b values within the study area. The northwestern and southeastern regions exhibit higher b values. Along the Haiyuan fault zone, the central rupture zone of the Haiyuan earthquake has relatively higher b values than other regions of this fault zone, which is possibly related to the sufficient release of stress during the main rupture of the Haiyuan earthquake. The b values vary from high in the west to low in the east along the Zhongwei fault. On the West Qinling fault zone, the epicenter of the recent Minxian-Zhangxian earthquake is associated with a low b value. In general, regions with low b values correspond well to areas with moderate-strong seismic events in the past 50 years. The spatial differences in b values may reflect variances in seismic hazards among fault zones and regions within the same fault zone.

Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Effect of Liver Segments and Hepatic Fibrosis Grade on Repeatability, Reliability, and Diagnostic Efficiency of Intravoxel Incoherent Motion.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is considered a potential marker of hepatic fibrosis (HF). OBJECTIVE: To explore the influencing factors of repeatability and reliability in IVIM-DWI parameters of ROI-based liver segments in participants with HF and healthy volunteers (HV) and to assess the diagnostic efficiency of these parameters in HF. METHODS: Participants with early HF (EHF, n=59) or advanced HF (AHF, n=38) and HV (n=48) were recruited. Two examiners measured IVIM data using mono-, bi-exponential and stretched exponential models. The results and influencing factors of repeatability and reliability of IVIM-DWI, and the diagnostic efficiency were analyzed. RESULTS: The repeatability of D* (CV: 26.62-41.47%) and DDC (CV: 18.01-34.40%) was poor, the repeatability of ADC (CV: 4.95-9.76%), D (CV: 7.09-15.52%), f (CV: 9.35-17.15%), and α (CV: 7.48-13.81%) was better; ordered logistic regression showed statistically significant results of IVIM-derived parameters; the reliability showed no obvious trend, and ordered logistic regression showed statistically significant results of IVIMderived parameters, groups, and partial hepatic segments (all p<0.001). IVIM-derived parameters with relatively good repeatability (CV<20%) and reliability (ICC>0.4) were used to establish regression models for differential diagnosis. The AUC of regression models was 0.744-0.783 (EHF vs. AHF), but no statistically significant parameters were found in the HV vs EHF comparison. CONCLUSION: IVIM-derived parameters were the most important factors affecting the repeatability and reliability, while staging of HF and hepatic segments may be the influencing factors of reliability. IVIM-derived parameters showed medium diagnostic efficiency in distinguishing between EHF and AHF.

Mixed-Zero-Sum-Game-Based Memory Event-Triggered Cooperative Control of Heterogeneous MASs Against DoS Attacks.

This article studies the problem of memory event-triggered cooperative adaptive control of heterogeneous nonlinear multiagent systems (MASs) under denial-of-service (DoS) attacks based on the multiplayer mixed zero-sum (ZS) game strategy. First, a neural-network-based reinforcement learning scheme is structured to obtain the Nash equilibrium solution of the proposed multiplayer mixed ZS game scheme. Then, a memory-based event-triggered mechanism considering the historical data is proposed. This effectively avoids incorrect triggering information caused by unknown external factors. Moreover, thanks to the idea of switching topology, the mixed ZS game problem under the influence of node-based DoS attacks is solved efficiently. In accordance with the Lyapunov stability theory, it is proved that all signals of heterogeneous MASs are bounded, all heterogeneous followers can track the trajectory of the leader during the no-attack period, the attacked follower can achieve stabilization control during the attack period, and the remaining nonattacked followers can achieve cooperative control during the attack period. Finally, the effectiveness of the designed memory-event-triggered-based mixed ZS game cooperative control strategy is tested by the given simulation results.

Adaptive Synaptic Scaling in Spiking Networks for Continual Learning and Enhanced Robustness.

Synaptic plasticity plays a critical role in the expression power of brain neural networks. Among diverse plasticity rules, synaptic scaling presents indispensable effects on homeostasis maintenance and synaptic strength regulation. In the current modeling of brain-inspired spiking neural networks (SNN), backpropagation through time is widely adopted because it can achieve high performance using a small number of time steps. Nevertheless, the synaptic scaling mechanism has not yet been well touched. In this work, we propose an experience-dependent adaptive synaptic scaling mechanism (AS-SNN) for spiking neural networks. The learning process has two stages: First, in the forward path, adaptive short-term potentiation or depression is triggered for each synapse according to afferent stimuli intensity accumulated by presynaptic historical neural activities. Second, in the backward path, long-term consolidation is executed through gradient signals regulated by the corresponding scaling factor. This mechanism shapes the pattern selectivity of synapses and the information transfer they mediate. We theoretically prove that the proposed adaptive synaptic scaling function follows a contraction map and finally converges to an expected fixed point, in accordance with state-of-the-art results in three tasks on perturbation resistance, continual learning, and graph learning. Specifically, for the perturbation resistance and continual learning tasks, our approach improves the accuracy on the N-MNIST benchmark over the baseline by 44% and 25%, respectively. An expected firing rate callback and sparse coding can be observed in graph learning. Extensive experiments on ablation study and cost evaluation evidence the effectiveness and efficiency of our nonparametric adaptive scaling method, which demonstrates the great potential of SNN in continual learning and robust learning.

Efficacy and safety of Pien Tze Huang capsules in patients with herpes zoster: A multicenter, randomized, double-blinded, and placebo-controlled trial.

BACKGROUND: Herpes zoster (HZ) is a common medical condition accompanied by several distressing symptoms, including acute pain. Pien Tze Huang (PZH) is a well-known traditional Chinese medicine (TCM) with numerous pharmacological effects, including antiviral properties, neuroprotection, and immunity regulation. PURPOSE: To investigate the efficacy and safety of PZH capsules in patients with HZ. STUDY DESIGN: A multicenter, double-blinded, randomized, and placebo-controlled trial from 8 hospitals in 5 cities of China. METHODS: Eligible participants were randomly assigned to the PZH capsule and placebo group at a 1:1 ratio. Treatment was conducted for 14 days with a window period of no more than 2 days. For the first 7 days, participants received antiviral drugs combined with PZH capsules (0.6 g/time, 3 times a day) or placebos. For the remaining 7 days, they were only treated with PZH capsules (0.6 g/time, 3 times a day) or placebos. RESULTS: We included 222 patients in the full analysis set (FAS), and 187 patients in the per protocol set (PPS). The change of numeric rating scale pain scores from baseline to the seventh day (±1 day) after treatment in the PZH capsule group was statistically superior to the placebo group (FAS: 2.33 vs. 1.71, 97.5%CI: 0.03 ∼ 1.19; PPS: 2.29 vs. 1.51, 97.5%CI: 0.18 ∼ 1.38). In the PPS, there was a significant difference in the time (days) of pain relief between the placebo group and the PZH capsule group (Mean (SD): 5.71 (3.76) vs. 4.69 (3.57), p = 0.046). On the seventh day (±1 day) after treatment, the level of CD8+ cells in the PZH capsule group were higher than those of the placebo group (FAS: Mean (SD): 24.08 (6.81) vs. 21.93 (8.19), p = 0.007; PPS: Mean (SD): 24.26 (6.93) vs. 22.15 (8.51), p = 0.012). The level of cytotoxic lymphocyte cells found similar results on the seventh day (±1 day) (FAS: Mean (SD): 12.17 (4.65) vs. 10.55 (4.15), p = 0.018; PPS: Mean (SD): 12.25 (4.65) vs. 10.11 (3.93), p = 0.002). No serious adverse events were noted and PZH capsules were well tolerated. CONCLUSION: PZH capsules confer therapeutic effects on HZ with the TCM symptom of stagnated heat of liver channel by substantially reducing the pain intensity, shortening the time of pain relief as well as regulating the immune function. On the basis of the efficacy and safety profiles, PZH capsules may be a promising complementary therapy for the treatment of HZ.

The feasibility of dexmedetomidine-led anesthesia maintenance strategy during major abdominal surgery.

Background: Dexmedetomidine is known for its selective action on α2-adrenoceptor sites and is recognized for its neuroprotective capabilities. It can improve postoperative cognitive function. Commonly used anesthetics, such as sevoflurane and propofol, have been reported to affect postoperative cognitive function. Therefore, it could be valuable to explore dexmedetomidine-led anesthesia strategy. This study was designed to assess the performance, safety, and effective infusion rate in anesthesia maintenance, to explore a feasible dexmedetomidine-led anesthesia maintenance protocol, and to provide a foundation for potential combined anesthesia. Methods: Thirty patients aged 18-60 years, classified as ASA I or II, undergoing abdominal surgery were involved. The anesthesia maintenance was achieved with dexmedetomidine, remifentanil and rocuronium. Dixon up-and-down sequential methodology was utilized to ascertain the ED50 of dexmedetomidine for maintaining Patient State Index (PSI) 25-40 (depth of stage III anesthesia). Intraoperative HR, BP and depth of anesthesia were monitored and controlled. The wake-up time from anesthesia, the incidence of intraoperative awareness and postoperative delirium, and the patients' satisfaction were assessed. Results: The results indicated that dexmedetomidine-led anesthesia could maintain the depth of stage III anesthesia during abdominal surgery. The ED50 and ED95 of dexmedetomidine infusion rates during anesthesia maintenance were 2.298 µg/kg·h (95%CI: 2.190-2.404 µg/kg·h) and 3.765 µg/kg·h (95%CI: 3.550-4.050 µg/kg·h). Continuous infusion of dexmedetomidine and 0.1-0.3 µg/kg·min remifentanil could maintain PSI 25-40, and provide appropriate anesthesia depth for abdominal surgery. Perioperative bradycardia and hypertension could be rapidly corrected with atropine and nitroglycerin. The median wake-up time after anesthesia was 4.8 min, the perioperative maximum HR had significant correlation with wake-up time and intraoperative dexmedetomidine dose. No intraoperative awareness and postoperative delirium occurred; the patients were satisfied with dexmedetomidine-led anesthesia. Conclusions: dexmedetomidine-led strategy could maintain stable depth of anesthesia throughout surgery, and the ED50 of dexmedetomidine infusion rates was 2.298 µg/kg·h. Intraoperative HR, BP and depth of anesthesia require monitoring, the bradycardia and hypertension could be rapidly corrected.