Research Progress on the Experimental Model and Underlying Mechanistic Studies of Tension-Type Headaches.

PURPOSE OF REVIEW: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH. RECENT FINDINGS: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches.

[Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure].

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

[Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure].

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.

[Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules].

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

[Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina].

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Integration of CuS/ZnIn2S4 flower-like heterojunctions and (MnCo)Fe2O4 nanozyme for signal amplification and their application to ultrasensitive PEC aptasensing of cancer biomarker.

Vascular endothelial growth factor 165 (VEGF165) is a crucial regulator of angiogenesis and works as a major protein biomarker of cancer metastasis. Therefore, its quantitative detection is pivotal in clinic. In this work, CuS/ZnIn2S4 flower-like heterojunctions had strong and stable photocurrents, which behaved as photoactive material to construct a photoelectrochemical (PEC) aptasensor for detecting VEGF165, combined by home-prepared (MnCo)Fe2O4 nanozyme-mediated signal amplification. The interfacial photo-induced electron transfer mechanism was chiefly discussed by UV-vis diffuse reflectance spectroscopy in details. Specifically, the (MnCo)Fe2O4 modified VEGF165 aptamer was released from the PEC aptasensing platform for its highly specific affinity to target VEGF165, which terminated the color precipitation reaction, ultimately recovering the PEC signals. The developed sensor displayed a wider linear range from 1 × 10-2 to 1 × 104 pg mL-1 with a smaller limit of detection (LOD) of 0.1 fg mL-1. This study provides some valuable insights for building other ultrasensitive aptasensors for clinical assays of cancer biomarkers in practice.

Hollow SnO2/CdS QDs/CdCO3 heterostructured nanocubes coupled with hollow PtPd/MnCo-CeO2 nanozyme-mediated synergistic amplification for ultrasensitive PEC immunoanalysis of lung cancer biomarker.

Nowadays, lung cancer is one of the most dangerous cancers threatening human life all over the world. As a crucial biomarker, cytokeratin 19 fragment 21-1 (CYFRA 21-1) is extraordinary important for diagnosis of non-small cell lung cancer (NSCLC). In this work, we synthesized hollow SnO2/CdS QDs/CdCO3 heterostructured nanocubes with high and stable photocurrents, which applied to construction of a sandwich-typed photoelectrochemical (PEC) immunosensor for detection of CYFRA 21-1, integrated by in-situ catalytic precipitation strategy with home-built PtPd alloy anchored MnCo-CeO2 (PtPd/MnCo-CeO2) nanozyme for synergistic amplification. The interfacial electron transfer mechanism upon visible-light irradiation was investigated in details. Further, the PEC responses were seriously quenched by the specific immunoreaction and precipitation catalyzed by the PtPd/MnCo-CeO2 nanozyme. The established biosensor showed a wider linear range of 0.001-200 ng mL-1 and a lower limit of detection (LOD = 0.2 pg mL-1, S/N = 3), coupled by exploring such analysis even in diluted human serum sample. This work opens a constructive avenue to develop ultrasensitive PEC sensing platforms for detecting diverse cancer biomarkers in clinic.

Ultrasensitive PEC cytosensor for breast cancer cells detection and inhibitor screening based on plum-branched CdS/Bi2S3 heterostructures.

Breast cancer is the most common malignant tumor in women, which seriously threatens the life and health of patients. Therefore, facile and sensitive detection of human breast cancer cells is crucial for cancer diagnosis. In this work, plum-branched CdS/Bi2S3 heterostructures (CdS/Bi2S3 HSs) were synthesized under hydrothermal condition, whose photoelectrochemical (PEC) property and biocompatibility were scrutinously investigated. In parallel, a signal amplification strategy was designed based on immune recognition between epidermal growth factor receptor (EGFR) overexpressed on membrane of breast cancer cells MDA-MB-231 and its aptamer. Integration of the above together, a highly sensitive PEC cytosensor was developed for analysis of target MDA-MB-231 cells, exhibiting a wider linear range of 1 × 102 âˆ¼ 3 × 105 cells mL-1 with a limit of detection (LOD) down to 6 cells mL-1 (S/N = 3). Further, the biosensor was explored for anticancer drug (e.g., dacomitinib) screening by monitoring the variations in the PEC signals of the expressed EGFR upon drug stimulation. The obtained CdS/Bi2S3 HSs are identified as promising and feasible photoactive material for determination of cancer cells and drug screening in clinic and related research.

Z-scheme Cu2MoS4/CdS/In2S3 nanocages heterojunctions-based PEC aptasensor for ultrasensitive assay of fumonisin B1 via signal amplification with hollow PtPd-CoSnO3 nanozyme.

Fumonisin B1 (FB1), the most prevalent and highest toxicity mycotoxins among fumonisins family, poses threats to human especially children and infants even at a trace level. Therefore, its facile and sensitive detection is of importance. Herein, Z-scheme Cu2MoS4/CdS/In2S3 nanocage-like heterojunctions (labeled Cu2MoS4/CdS/In2S3) were synthesized, whose photoelectrochemical (PEC) property and electron transfer mechanism were strictly investigated. The Cu2MoS4/CdS/In2S3 behaved as photoactive substrate for building a PEC sensing platform for detection of FB1, integrated with PtPd alloy modified hollow CoSnO3 nanoboxes (labeled PtPd-CoSnO3) nanozyme. By virtue of the stronger affinity between the target FB1 and its aptamer (FB1-Apt), the photocurrent was recovered by releasing the CoSnO3-PtPd3 modified FB1-Apt (FB1-Apt/PtPd-CoSnO3) from the photoanode, which can terminate the catalytic precipitation reaction for its peroxidase-like property. The resultant PEC aptasensor exhibited a wider dynamic linear range from 1 × 10-4 to 1 × 102 ng mL-1 with a lower limit of detection (0.0723 pg mL-1). Thus, this research provides a feasible PEC sensing platform for routine analysis of other mycotoxins in practice.

Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.

The gut microbiota is increasingly considered to play a key role in human immunity and health. The aging process alters the microbiota composition, which is associated with inflammation, reactive oxygen species (ROS), decreased tissue function, and increased susceptibility to age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on the gut microbiota, particularly in reducing pathogenic bacteria abundance and increasing beneficial bacteria populations. However, there is limited evidence of the effect of plant polysaccharides on age-related gut microbiota dysbiosis and ROS accumulation during the aging process. To explore the effect of Eucommiae polysaccharides (EPs) on age-related gut microbiota dysbiosis and ROS accumulation during the aging process of Drosophila, a series of behavioral and life span assays of Drosophila with the same genetic background in standard medium and a medium supplemented with EPs were performed. Next, the gut microbiota composition and protein composition of Drosophila in standard medium and the medium supplemented with EPs were detected using 16S rRNA gene sequencing analysis and quantitative proteomic analysis. Here, we show that supplementation of Eucommiae polysaccharides (EPs) during development leads to the life span extension of Drosophila. Furthermore, EPs decreased age-related ROS accumulation and suppressed Gluconobacter, Providencia, and Enterobacteriaceae in aged Drosophila. Increased Gluconobacter, Providencia, and Enterobacteriaceae in the indigenous microbiota might induce age-related gut dysfunction in Drosophila and shortens their life span. Our study demonstrates that EPs can be used as prebiotic agents to prevent aging-associated gut dysbiosis and reactive oxidative stress.

N-3 polyunsaturated fatty acids protect esophageal epithelial cells from acid exposure.

Our previous study showed that n-3 PUFAs inhibited inflammation in rats with esophagitis. This study aimed to observe the protective effect of n-3 PUFAs against acid damage to esophageal epithelial cells (Het-1A cells) and to explore its mechanism. The level of malondialdehyde (MDA) was increased by acid exposure, while that of superoxide dismutase (SOD) was decreased. In groups with different ratios of n-6/n-3 PUFAs, the expression levels of nuclear factor E2 related factor 2 (Nrf2) and SOD were increased with increasing proportions of n-3 PUFAs and were highest in the 1:1 group. Compared with those in the 9:1 group, the expression of NOD like receptor pyrin domain-containing protein 3 (NLRP3) and caspase-1 and the pyroptosis rate in the 1:1 group were decreased. Intervention with an Nrf2 agonist increased the expression of Nrf2 and decreased the expression of NLRP3 and caspase-1 and the pyroptosis rate. However, inhibiting Nrf2 expression led to the opposite result. In conclusion, n-3 PUFAs protected esophageal epithelial cells from acid damage by upregulating Nrf2 expression, which disrupted oxidative stress and NLRP3 inflammasome activation and inhibited pyroptosis.

[Medication rule of traditional Chinese medicine for heart failure after myocardial infarction: based on data mining].

This study aims to explore the medication rule of traditional Chinese medicine(TCM) for heart failure after myocardial infarction via data mining. To be specific, articles on the treatment of the disease with Chinese medicine were retrieved from CNKI, Wanfang, VIP, and SinoMed and related information was collected. A database was created with Microsoft Excel 2019, and SPSS Clementine 12.0 and IBM SPSS Statistics 23.0 were applied for association rules analysis, cluster analysis, and factor analysis. Finally, a total of 81 TCM prescriptions were screened out, involving 91 medicinals with cumulative use frequency of 740. The main syndromes were Qi deficiency and blood stasis, Yang Qi deficiency and blood stasis together with retained morbid fluid, deficiency of both Qi and Yin and blood stasis. The medicinals with high-frequency were Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Poria, and Aconiti Lateralis Radix Praeparata. The effects of the medicinals were tonifying deficiency, activating blood and resolving stasis, and promoting urination and draining dampness. The association rules analysis yielded "Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma" "Astragali Radix-Aconiti Lateralis Radix Praeparata-Salviae Miltiorrhizae Radix et Rhizoma" "Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix" combinations. Cluster analysis yielded 6 basic formulas for heart failure after myocardial infarction. Factor analysis extracted a total of 8 common factors. Heart failure after myocardial infarction is characterized by the syndrome of deficiency in nature and excess in superficiality. The core pathogenesis is "deficiency" "stasis" "retained morbid fluid", particularly "deficiency". This disease is closely related to the heart, lung, and spleen. The basic treatment principle is replenishing Qi and activating blood, and warming Yang, excreting water, and nourishing yin should also be emphasized. The common basic prescriptions, such as Siwu Decoction, Shengmai Powder, Xuefu Zhuyu Decoction, Linggui Zhugan Decoction, and Shenfu Decoction, have been discovered. This study provided data for clinical medication and drug development for heart failure after myocardial infarction.

Variation in quality of the different prepared formulation granules of rhubarb was evaluated by quantitative analysis of multicomponents with single marker.

Rhei Radix et Rhizoma formula granule (RRFG) , Winy Rhei Radix et Rhizoma formula granule(WRFG) and Rhubarb charcoal formula granules (RCFG) are the three most popular and effective formula granules of rhubarb in China and anthraquinone components are their main active ingredients. In order to discuss the difference in anthraquinone components of these three drugs, a simultaneous quantitative analysis method of multicomponents by single-marker (QAMS) was developed. Emodin was chosed as the internal reference standard, the relative correction factors (RCFs) of aloe-emodin, rhein, chrysophanol and physcion were established and the contents of the four components were calculated based on the RCFs, respectively. Meanwhile, the contents of these components was determined by external standard method (ESM) and compared with QAMS to verify its rationality, feasibility and repeatability. The results showed that there were no significant difference between QAMS and ESM (RSDs≤2.26%). The contents of anthraquinone components showed a wide variation in these three drugs. All of 5 components were higher in RRFG than that in the others and RCFG had the lowest content. This method was successfully applied for the evaluation on difference of these drugs and the wide variation in anthraquinone components indicated there were different pharmacodynamic basis.

Novel Ultrasensitive Photoelectrochemical Cytosensor Based on Hollow CdIn2S4/In2S3 Heterostructured Microspheres for HepG2 Cells Detection and Inhibitor Screening.

Hepatocellular carcinoma is a life-threatening malignant tumor found around the world for its high morbidity and mortality. Therefore, it is of great importance for sensitive analysis of liver cancer cells (HepG2 cells) in clinical diagnosis and biomedical research. To fulfill this demand, hollow CdIn2S4/In2S3 heterostructured microspheres (termed CdIn2S4/In2S3 for clarity) were prepared by a two-step hydrothermal strategy and applied for building a novel photoelectrochemical (PEC) cytosensor for ultrasensitive and accurate detection of HepG2 cells through specific recognition of CD133 protein on the cell surface with the respective aptamer. The optical properties of CdIn2S4/In2S3 were investigated by UV-vis diffuse reflectance spectroscopy (DRS) and PEC technology. By virtue of their appealing PEC characteristics, the resultant PEC sensor exhibited a wider dynamic linear range from 1 × 102 to 2 × 105 cells mL-1 with a lower limit of detection (LOD, 23 cells mL-1), combined by evaluating the expression level of CD133 protein stimulated by metformin as a benchmarked inhibitor. This work opens a valuable and feasible avenue for sensitive detection of diverse tumor cells, holding great potential in early clinical diagnosis and treatment coupled by screening inhibitors.

Heterostructured BiVO4/CoPi nanoarrays as high-efficiency photoanode and AuPt nanodendrites as nanozyme for sensitive sensing of miRNA 141.

MicroRNA (miRNA) is a new class of tumor biomarkers in human body for early diagnosis and therapy of cancers, whose detection has scientific significance and potential applications. Herein, a sensitive heterostructured BiVO4/CoPi photoelectrochemical (PEC) biosensor was established for sensing miRNA 141 with assistance of home-synthesized AuPt nanodendrites (NDs) as nanozyme. Specifically, the BiVO4/CoPi heterostructures displayed rough worm-like internetworks, as characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). In parallel, the PEC and UV-vis diffuse reflectance spectroscopy tests confirmed their excellent optical property, combined by discussing the interfacial electron transfer mechanism. Additionally, the AuPt NDs displayed superior peroxidase-like property in the presence of H2O2 as identified by benchmarked tetramethylbenzidine (TMB) oxidation, coupled by showing remarkable catalysis for 3-amino-9-ethylcarbazole (AEC) oxidation to form biocatalytic precipitation (BCP). Integrated by a cyclic enzyme strategy, the developed PEC biosensor exhibited a wider linear range of 5 fM ∼1 pM and a lower limit of detection (LOD) as low as 0.17 fM (S/N = 3). This work provides some valuable insights for sensitive analysis of tumor-associated miRNA in clinic.

Comparison of Pull and Introducer Techniques for Percutaneous Endoscopic Gastrostomy.

Objective: To compare indications, success rates and complications of pull [P] and introducer [I] techniques for percutaneous endoscopic gastrostomy (PEG). Methods: In this retrospective study, inpatients who underwent primary PEG tube insertion between January 2015 and February 2020 at the Endoscopy Center of the First Affiliated Hospital of Fujian Medical University were included. Results: A total of 103 inpatients were included in this study (P group, n = 67; I group, n = 36). The rates of tube replacement within first six months in the P and I groups were 1.5% and 11.1%, respectively (P = 0.049). The most common primary indication of PEG was malignancy. The proportion of patients with esophageal cancer was significantly lower in the P group (24.4% vs 54.2%, P = 0.015). No significant difference was found in the overall, major, or minor complications between the two groups. In patients with esophageal stenosis, the pull method was a risk factor for complications (P = 0.03; odds ratio [OR] = 12, 95% confidence interval [CI]: 1.164-123.684). Logistic regression analysis showed that the risk factors for major and minor complications were the admission-to-gastrostomy interval (OR = 1.078, 95% CI: 1.016-1.145, P = 0.014) and lack of antibiotic use (OR = 4.735, 95% CI: 1.247-17.979, P = 0.022), respectively. Conclusion: Both PEG techniques have high clinical success rates. The introducer technique is more suitable for patients with esophageal stricture, which has lower minor complications, but higher rate of tube replacement compared to the pull technique. Use of antibiotics may reduce minor complications following PEG. Early PEG insertion may help to reduce post-PEG major complications.

Registration of intervention trials of Traditional Chinese Medicine for four neurological diseases on Chinese Clinical Trial Registry and ClinicalTrials.gov: a narrative review.

OBJECTIVE: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases. METHODS: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data. RESULTS: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase IV. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results. CONCLUSIONS: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.

[Effects of cigarette smoke extract on mitochondrial function of macrophages].

Objective: To investigate the effects of cigarette smoke extract (CSE) on the mitochondrial function of macrophages. Methods: RAW264.7 macrophages were used for the experiment in this study. When the cell density was about 70%, the old culture medium was abandoned, and the 100% CSE stock solution was diluted with serum-free DMEM and FBS into 1%, 5%, 15%, 25% and 90% CSE and added to the well plate. The cell activity of RAW264.7 cells treated with CSE at different concentrations for 24 h was detected by CCK-8 method. Then the optimal CSE concentration was selected to treat cells for 0 h, 24 h, 48 h or 72 h respectively, and CCK-8 assay was used to detect the cell activity of CSE treated cells at different time groups. After the cells were treated with 0%, 5% and 25% CSE for 24 hours, cell necrosis and apoptosis was detected by Annexin V-FITC /PI staining; Mitochondrial membrane damage of RAW 264.7 was detected by mitochondrial membrane potential assay kit with JC-1; Macrophages were stained with ROS-specific dye DCFH-DA, and then Flow cytometer was used to determine the fluorescence and the proportion of ROS-positive macrophages; the enhanced ATP assay kit was used to detect the intracellular ATP concentration. Results: ①Compared with 0% CSE, cell viability was increased significantly in 1% CSE group (P＜0.01), cell viability was decreased significantly when CSE concentration was above 5% (P＜0.05); Macrophages were treated with 5% CSE, and cell viability was decreased significantly with the increase of treatment time (P＜0.01). ②Compared with 0% CSE, 5% CSE and 25% CSE mainly caused macrophage necrosis, decreased mitochondrial membrane potential, increased ROS production and decreased ATP significantly (P＜0.05 or P＜0.01), and the changes were more significant in 25% CSE treatment group(P＜0.05 or P＜0.01). Conclusion: CSE may affect mitochondrial function of macrophages, leading to decreased cell viability and necrosis.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention for tension-type headache in recent five years].

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.