Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.
PURPOSE: While Fear of progression (FoP) is a natural reaction in cancer, elevated FoP can impact life quality and social function. Our study aims to explore how illness perception, social support, and posttraumatic growth influence patients' FoP. METHODS: This study enrolled 243 young and middle-aged adults with digestive system cancer at a hospital in Guangzhou from November 2022 to November 2023. In this study, the measurement instruments utilized included The Fear of Progression Questionnaire-Short Form, The Brief Illness Perception Questionnaire, The 12-item Perceived Social Support Scale, and The 21-item Posttraumatic Growth Inventory. Data was analyzed employing polynomial regression and response surface analyses. RESULTS: The mean score of FoP was 35.45 ± 10.05, and 59.3% of the cancers (scores≥34) had clinically dysfunctional levels of FoP. Regarding congruence, patients' FoP was higher when the levels of illness perception and social support were both low or high than when the levels were both intermediate. Regarding incongruence, patients' FoP was lower when the level of illness perception was low and social support was high compared with when the level of illness perception was high and social support was low. Additionally, posttraumatic growth moderated the (in)congruence effect of illness perception-social support on the FoP of patients. CONCLUSIONS: Low or high illness perception-social support congruence was detrimental to the FoP of patients. Low illness perception-high social support incongruence was beneficial to patients' FoP. Posttraumatic growth can be a positive factor for enhancing the impact of low illness perception-high social support incongruence on patients' FoP.
The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.
OBJECTIVE: Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ. METHODS: Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed. RESULTS: The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages. CONCLUSION: In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.
INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.
Glycine is a nonessential amino acid that plays a vital role in various biological activities. However, the conventional synthesis of glycine requires sophisticated procedures or toxic feedstocks. Herein, we report an electrochemical pathway for glycine synthesis via the reductive coupling of oxalic acid and nitrate or nitrogen oxides over atomically dispersed Fe-N-C catalysts. A glycine selectivity of 70.7% is achieved over Fe-N-C-700 at -1.0 V versus RHE. Synergy between the FeN3C structure and pyrrolic nitrogen in Fe-N-C-700 facilitates the reduction of oxalic acid to glyoxylic acid, which is crucial for producing glyoxylic acid oxime and glycine, and the FeN3C structure could reduce the energy barrier of *HOOCCH2NH2 intermediate formation thus accelerating the glyoxylic acid oxime conversion to glycine. This new synthesis approach for value-added chemicals using simple carbon and nitrogen sources could provide sustainable routes for organonitrogen compound production.
Necroptosis, considered as a form of programmed cell death, contributes to neural loss. The 5-hydroxytryptamine 4 receptor (5-HT4R) is involved in neurogenesis in the enteric nervous system. However, whether the activation of 5-HT4R can alleviate diabetic enteric neuropathy by inhibiting receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is unclear. This study aimed to explore the beneficial effects of 5-HT4R agonist on enteric neuropathy in a mouse model of diabetes and the mechanisms underlying these effects. Diabetes developed neural loss in the colon of mice. 5-HT4Rs localized in submucosal and myenteric plexuses were confirmed. Administration of 5-HT4R agonist attenuated diabetes-induced colonic hypomotility and neural loss of the colon in mice. Remarkably, RIPK3, phosphorylated RIPK3, and its downstream target mixed lineage kinase domain-like protein (MLKL), two key proteins regulating necroptosis, were significantly up-regulated in the colon of diabetic mice. Treatment with 5-HT4R agonist appeared to inhibit diabetes-induced elevation of RIPK3, phosphorylated RIPK3, and MLKL in the colon of mice. Diabetes-induced up-regulation of MLKL in both the mucosa and the muscularis of the colon was prevented by Ripk3 deletion. Moreover, diabetes-evoked neural loss and delayed colonic transit were significantly inhibited by Ripk3 removal. These findings suggest that activation of 5-HT4Rs could potentially provide a protective effect against diabetic enteric neuropathy by suppressing RIPK3-mediated necroptosis.
Diabetes Mellitus, Experimental , Protein Kinases , Mice , Animals , Protein Kinases/metabolism , Serotonin/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Apoptosis , Phosphorylation/physiology
Since structural analyses and toxicity assessments have not been able to keep up with the discovery of unknown per- and polyfluoroalkyl substances (PFAS), there is an urgent need for effective categorization and grouping of PFAS. In this study, we presented PFAS-Atlas, an artificial intelligence-based platform containing a rule-based automatic classification system and a machine learning-based grouping model. Compared with previously developed classification software, the platform's classification system follows the latest Organization for Economic Co-operation and Development (OECD) definition of PFAS and reduces the number of uncategorized PFAS. In addition, the platform incorporates deep unsupervised learning models to visualize the chemical space of PFAS by clustering similar structures and linking related classes. Through real-world use cases, we demonstrate that PFAS-Atlas can rapidly screen for relationships between chemical structure and persistence, bioaccumulation, or toxicity data for PFAS. The platform can also guide the planning of the PFAS testing strategy by showing which PFAS classes urgently require further attention. Ultimately, the release of PFAS-Atlas will benefit both the PFAS research and regulation communities.
Artificial Intelligence , Fluorocarbons , Software , Machine Learning , Bioaccumulation , Fluorocarbons/toxicity
The radioresistance of glioma is an important cause of treatment failure and tumor aggressiveness. In the present study, under performed with linear accelerator, the effects of 0.3 and 3.0 Gy lowdose radiation (LDR) on the proliferation and migration of C6 glioma stem cells in vitro were examined by flow cytometric analysis, immunocytochemistry and western blot analysis. It was found that lowdose ionizing radiation (0.3 Gy) stimulated the proliferation and migration of these cells, while 3.0 Gy ionizing radiation inhibited the proliferation of C6 glioma stem cells, which was mediated through enhanced Wnt/ßcatenin signaling, which is associated with glioma tumor aggressiveness. LDR treatment increased the expression of the DNA damage marker γH2AX but promoted cell survival with a significant reduction in apoptotic and necrotic cells. When LDR cells were also treated with an inhibitor of Wnt receptor 1 (IWR1), cell proliferation and migration were significantly reduced. IWR1 treatment significantly inhibited Wnt1, Wnt3a and ßcatenin protein expression. Collectively, the current results demonstrated that IWR1 treatment effectively radiosensitizes glioma stem cells and helps to overcome the survival advantages promoted by LDR, which has significant implications for targeted treatment in radioresistant gliomas.
Glioma , beta Catenin , Humans , beta Catenin/genetics , Glioma/genetics , Glioma/radiotherapy , Glioma/metabolism , Wnt Signaling Pathway , Cell Survival , Cell Proliferation , Cell Line, Tumor
The health benefits of anthocyanins have attracted extensive research interest. However, anthocyanins are sensitive to certain environmental and gastrointestinal conditions and have low oral bioavailability. It has been reported that delivery systems made in different ways could improve the stability, bioavailability and bioactivity of anthocyanins. This present review summarizes the factors affecting the stability of anthocyanins and the reasons for poor bioavailability, and various technologies for encapsulation of anthocyanins including microcapsules, nanoemulsions, microemulsions, Pickering emulsions, nanoliposomes, nanoparticles, hydrogels and co-assembly with amphiphilic peptides were discussed. In particular, the effects of these encapsulation technologies on the stability, bioavailability and bioactivities of anthocyanins in vitro and in vivo experiments are reviewed in detail, which provided scientific insights for anthocyanins encapsulation methods. However, the application of anthocyanins in food industry as well as the biological fate and functional pathways in vivo still need to be further explored.
The coronavirus disease 2019 (COVID-19) has been associated with various psychological symptoms. We report a case of a female patient who was diagnosed with persistent insomnia and anxiety associated with COVID-19, which was successfully treated with nine treatment sessions of auricular acupuncture. This case report provides preliminary evidence to support further research into auricular acupuncture as a potential therapy for persistent insomnia and anxiety associated with COVID-19.
Introduction: Cognitive dysfunction has frequently been found in patients with migraine. The so-called contingent negative variation (CNV) and EEG power spectral densities may be the best choices to explore the underlining pathophysiology, such as cortical inhibition and habituation. Methods: Thirty migraine patients without aura and healthy controls matched for sex, age, and education were recruited separately for CNV recording. The amplitudes, latencies, and squares of different CNV components, such as oCNV, iCNV, tCNV, and PINV, were selected and analyzed. Behavioral data, such as manual reaction time (RT), were analyzed. We used the Person correlation coefficient R to analyze different ERP components in relation to clinical characteristics. A multiple regression analysis was conducted for the migraine group. Spectral analysis of EEG data from all channels using the fast Fourier transform (FFT). Results: The migraine group had longer A-latency, C-latency, and iCNV-latency than the control group. The migraine group had higher iCNV-amplitude, oCNV-amplitude, and tCNV-amplitude than the control group, especially those located in the occipital area. The iCNV-square, oCNV-square, tCNV-square, or PINV-square in the migraine group was significantly larger than the control group. Different correlations were found between clinical characteristics and ERP components. The delta or theta activity in the migraine group was statistically lower than in the control group. Discussion: Our study has revealed that migraine attacks may influence responsivity, pre-activation, habituation, and cortical inhibition not only on the behavioral level but also on the electrophysiological level. Abnormal changes in cortical habituation and inhibition can be interpreted as CNV components. Additionally, analyses have revealed correlations between CNV components and various factors, including age, the clinical course of the condition, attack frequency, pain intensity, and duration. Thus, repetitive migraine attacks can lead to a reduction in cortical inhibition and subsequent impairment in executive function.
Efficient electrode design is crucial for the electrochemical reduction of CO2 to produce valuable chemicals. The solution used for the preparation of electrodes can affect their overall properties, which in turn determine the reaction efficiency. In this work, we report that transition metal salts could induce the change of two-phase ionic liquid/ethanol mixture into miscible one phase. Pre-phase separation region near the phase boundary of the ternary system was observed. Zinc nanoparticles were electro-deposited along the fibres of carbon paper (CP) substrate uniformly in the salt-induced pre-phase separation region solution. The as-prepared Zn(1)/CP electrode exhibits super-wettability to the electrolyte, rendering very high catalytic performance for CO2 electro-reduction, and the Faradaic efficiency towards CO is 97.6% with a current density of 340 mA cm-2, which is the best result to date in an H-type cell.
Phosphorus (P) is a limiting nutrient in the soil-plant nutrient cycling. Although the exogenous application of chemical P fertilizers can satisfy crop P requirements during critical growth phases. While excessive P fertilizers use results in low phosphorus acquisition efficiency (PAE), it has serious environmental consequences and hastens the depletion of P mineral reserves. Phosphate-solubilizing bacteria (PSB) have the potential to make insoluble phosphate available to plants through solubilization and mineralization, increasing crop yields while maintaining environmental sustainability. Existing reviews mainly focus on the beneficial effects of PSB on crop performance and related mechanisms, while few of them elucidate the action mechanisms of PSB in soil-microbe-plant interactions for crop cultivation with high yield efficiency. Hence, this study provides a comprehensive review of the physicochemical and molecular mechanisms (e.g., root exudates, extracellular polysaccharides, organic acids, phosphatases, and phosphate-specific transport systems) of PSB to facilitate the P cycle in the soil-plant systems. Further, the potential of commercial applications of PSB (e.g., genetic engineering, seed priming and coating) are also discussed in order to highlight their contribution to sustainable agriculture. Finally, existing challenges and future prospects in agricultural applications are proposed. In conclusion, we firmly believe that PSB represent a highly significant biotechnological tool for enhancing agricultural productivity and offers a wide range of extensive potential applications.
The plant cell wall (CW) is one of the most important physical barriers that phytopathogens must conquer to invade their hosts. This barrier is a dynamic structure that responds to pathogen infection through a complex network of immune receptors, together with CW-synthesizing and CW-degrading enzymes. Callose deposition in the primary CW is a well-known physical response to pathogen infection. Notably, callose and cellulose biosynthesis share an initial substrate, UDP-glucose, which is the main load-bearing component of the CW. However, how these 2 critical biosynthetic processes are balanced during plant-pathogen interactions remains unclear. Here, using 2 different pathogen-derived molecules, bacterial flagellin (flg22) and the diffusible signal factor (DSF) produced by Xanthomonas campestris pv. campestris, we show a negative correlation between cellulose and callose biosynthesis in Arabidopsis (Arabidopsis thaliana). By quantifying the abundance of callose and cellulose under DSF or flg22 elicitation and characterizing the dynamics of the enzymes involved in the biosynthesis and degradation of these 2 polymers, we show that the balance of these 2 CW components is mediated by the activity of a ß-1,3-glucanase (BG2). Our data demonstrate balanced cellulose and callose biosynthesis during plant immune responses.
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Innate Immunity Recognition , Glucans/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cellulose/metabolism , Plant Immunity
BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.
Headache Disorders, Secondary , Migraine Disorders , Tension-Type Headache , Trigeminal Autonomic Cephalalgias , Adult , Humans , Cross-Sectional Studies , Headache , Tension-Type Headache/diagnosis , Tension-Type Headache/drug therapy , Tension-Type Headache/epidemiology , China/epidemiology , Headache Disorders, Secondary/diagnosis , Headache Disorders, Secondary/epidemiology , Headache Disorders, Secondary/prevention & control
Photothermal interfacial evaporation with low cost and environmental friendliness has attracted much attention. However, there are still many problems with this technology, such as heat loss and salt accumulation. Due to their different structures and adjustable chemical composition, electrospun nanofiber materials generally exhibit some unique properties that provide new approaches to address the aforementioned issues. In this review, the rational design principles for improving the total efficiency of solar evaporation are described for thermal/water management systems and salt-resistance strategies. And we review the state-of-the-art advancements in photothermal evaporation based on nanofiber materials and discuss their derivative applications in desalination, water purification, and power generation. Finally, we highlight key challenges and opportunities in both fundamental research and practical applications to inform further developments in the field of interfacial evaporation.
Background: Acupuncture is considered as a potential treatment option for primary tinnitus, as there is a lack of conventional therapies with well-established efficacy. However, there are limited studies that compare the effectiveness of different acupuncture therapies. Thus, this systematic review and network meta-analysis protocol aims to compare the efficacy of various acupuncture-related therapies for primary tinnitus, and determine the optimal treatment. Methods: A comprehensive search of 10 representative databases will be conducted to identify eligible randomized controlled trials (RCTs) regarding multiple acupuncture-related therapies for primary tinnitus. Two independent researchers will extract data individually, and the methodological quality of each RCT will be assessed using Cochrane's risk of bias 2.0 tool. Standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted, and WinBUGS V.1.4.3 and R 3.6.2 software will be adopted to synthesize network data and generate relevant graphs. Subgroup analyses, sensitivity analyses, and assessment of publication bias will be conducted as appropriate. Discussion: This study's results are anticipated to identify the optimal acupuncture technique for treating primary tinnitus, thereby providing evidence-based clinical decisions for patients and clinicians to select the most effective acupuncture treatment. Prospero Registration Number: CRD42023399621.
Introduction: Herpes zoster (HZ) can adversely influence patients' quality of life and sometimes it can develop postherpetic neuralgia (PHN). To date, it remains challenging to be managed by currently available therapies. Intradermal acupuncture (IDA) has the potential to be an adjunctive therapy for acute HZ and infrared thermography (IRT) may be useful for predicting PHN; however, current evidence remains inconclusive. Therefore, the purposes of this trial are to 1) evaluate the efficacy and safety of IDA as an adjunctive therapy for acute HZ; 2) to explore the feasibility of IRT for early prediction of PHN and as an objective tool to aid in subjective pain assessment in acute HZ. Methods: This study is designed as a randomized, parallel-group, sham-controlled, and patient-assessor-blinded trial, including 1-month treatment and 3-month follow-ups. Seventy-two qualified participants will be randomly split into the IDA or sham IDA group in a ratio of 1:1. Apart from standard pharmacological treatments in both groups, the two groups will receive 10 sessions of IDA or sham IDA, respectively. Primary outcome measures are the visual analog scale (VAS), indicators of herpes lesions' recovery, the temperature of the pain area, and the incidence rate of PHN. The secondary outcome is the 36-item Short Form Health Survey (SF-36). Indicators of herpes lesions' recovery will be assessed at each visit and follow-ups. The remaining outcomes will be assessed at baseline, 1 month after intervention, and 3-month follow-up. Safety evaluation will be determined by adverse events during the trial. Conclusion: Expected results will determine whether IDA can enhance therapeutic effectiveness of pharmacotherapy for acute HZ with acceptable safety profile. In addition, it will verify the accuracy of IRT for early prediction of PHN and as an objective tool of subjective pain for acute HZ. Trial Registration: Clinicaltrials.gov (identification number: NCT05348382; Registered 27 April 2022, https://clinicaltrials.gov/ct2/show/NCT05348382).
