Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Uncovering quality markers of Yiqi-Tongluo capsule against myocardial ischemia and optimization of its extraction process.

Myocardial ischemia (MI), a condition in which the heart is unable to function due to insufficient blood and oxygen supply, is a major cause of death from coronary heart disease (CHD). Yiqi Tongluo capsule (YTC) is a Chinese patent drug which commonly used for treatment of MI in clinic. However, the related active components of YTC for treatment of MI were still uncovered. This paper is aimed to study the quality markers (Q-markers) of YTC and further optimize the extraction process of YTC based on Q-markers, providing research foundation for the further modern pharmaceutical preparations of YTC. We firstly used UPLC-QTOF-MS to analyze the constituents of YTC absorbed in blood, then isoprenaline (ISO) induced H9c2 cell model was used further screen the active constituents with protective effects on cardiomyocytes. After that, the orthogonal table (L9 (34)) was used to optimize the extraction process with three levels of 4 factors (water addition, immersion time, extraction time and decoction times). Finally, the HPLC fingerprint of 15 batches of optimized YTC was established. In our present study, a total of 33 components were identified in YTC, of which 10 components were absorbed in blood. Among the 10 components, 8 compounds had significant protective effects on ISO stimulated H9c2 cells, including Paeoniflorin, Ferulic acid, Calycosin, Senkyunolide A, N-butylphthalide, Z-ligustilide, LevistilideA, and Astragaloside IV, which were considered as the Q-markers of YTC. The optimized extraction process based on Q-marker as follows: soaking 1 h, then adding 8 times water to extract 3 times by decoction, each extraction lasts 1.5 h. The HPLC fingerprint of optimized YTC was established with 15 batches of YTC samples, and the optimized YTC samples has no significant toxicity to the heart, liver, spleen, lungs, and brain tissues of rats.

Integrating network pharmacology and experimental studies for uncovering the molecular mechanisms of Dioscorea bulbifera L. in the treatment of thyroid cancer.

Introduction: Thyroid cancer (TC), a common endocrine malignant tumor with a higher incidence in females than in males, is a serious threat to human life and health. Although current clinical treatments can alleviate this disease, the recurrence rate remains high. Tuber Dioscoreae Bulbiferae, also called Huang-Yao-Zi (HYZ), has remarkable curative properties, few side effects and is used for the treatment of sore throat, goiter, hemoptysis, and other diseases in traditional Chinese medicine (TCM). Existing clinical studies have found that HYZ can improve the clinical symptoms of TC patients and reduce tumor volume, while in vitro studies have found that HYZ can induce the death of thyroid cancer cells. However, the mechanism of HYZ in the treatment of TC is still unclear. Methods: In this study, based on network pharmacology and bioinformatics, the target and molecular mechanism of HYZ in the treatment of TC were preliminarily explored. The results suggest that the antithyroid cancer effect of HYZ may be related to the PI3K-Akt and focal adhesion pathways. Then, a TC cell model was established to further explore the detail molecular mechanisms. Results: Fortunately, HYZ induced apoptosis in KMH-2 cells and regulated the expression of apoptosis-related proteins and genes. At the same time, HYZ can also significantly inhibit the migration and invasion of TC cells. Further studies showed that the pharmacological activities of HYZ were related to the regulation of the PI3K-Akt and focal adhesion pathways. Conclusion: Our study provides a reference for further animal or clinical studies investigating the effectiveness and molecular mechanisms of HYZ against thyroid cancer.

Association between urinary metal concentrations and abnormal estimated glomerular filtration rate in Chinese community-dwelling elderly: Exploring the mediating effect of triglycerides.

BACKGROUND: Environmental metal exposure is associated with elevated triglycerides (TG) and the development of chronic kidney disease (CKD). However, the relationship between metal exposure and glomerular filtration rate (GFR) remains uncertain, and the mediating effect of TG between the two is unclear. METHODS: This study measured the concentrations of 14 metals in urine samples from 3752 elderly people in the community. The most relevant metals were screened by least absolute shrinkage and selection operator (LASSO) regression. The relationship between combined exposure to multiple metals and abnormal estimated glomerular filtration rate (eGFR) was explored using multivariate logistic regression analysis and Bayesian kernel machine regression (BKMR) analysis. Generalized linear regression models and the Karlson-Holm-Breen (KHB) method were used to assess the mediating effects of TG. RESULTS: In the single-metal model, calcium (Ca), iron (Fe), selenium (Se), strontium (Sr), and thallium (Tl) showed significant negative correlations with the prevalence of abnormal eGFR (all P < 0.05). In the multi-metals model, Ca, Se, and Tl continued to show significant negative correlations, while vanadium (V) and zinc (Zn) showed significant positive correlations with abnormal eGFR (all P < 0.05). The BKMR model showed a negative joint effect of the mixture of Ca, V, Zn, Se, and Tl on the prevalence of abnormal eGFR. The generalized linear regression model showed a significant positive correlation between the concentrations of Ca (ß = 0.07), Zn (ß = 0.07), Se (ß = 0.09), and TG levels (all P < 0.05). In the mediation analysis, TG masked a 4.30% and 5.21% correlation between Ca and Se and the prevalence of eGFR abnormalities, respectively. CONCLUSIONS: Urinary concentration of multiple metals is significantly associated with eGFR abnormalities, and Ca, and Se may be among the potential protective factors. TG masked some of the protective effects of Ca and Se.

Immediate effect in retina and choroid after 650 nm low-level red light therapy in children.

INTRODUCTION: To investigate the changes in the retina and choroid of children after 650 nm low-level red light therapy (LLRLT). METHODS: In this prospective study, 25 subjects in the Shanghai Eye and ENT Hospital of Fudan University were included from August 2021 to September 2021. One eye was randomly selected to receive LLRLT for 3 minutes. Swept-source optical coherence tomography (OCT) and OCT angiography (OCTA) were used to measure retinal fovea perfusion density (RFPD), retinal fovea thickness (RFT), choroidal fovea blood flow (CFBF), and choroidal fovea thickness (CFT) before LLRLT, 5 minutes and 1 hour after LLRLT. Baseline characteristics between LLRLT and non-LLRLT eyes were compared. Changes in the retinal and choroidal parameters were analyzed by ANCOVA models. SAS software was used for data analysis. The difference was considered statistically significant if p < 0.05. RESULTS: There was no difference in baseline characteristics between LLRLT eyes and non-LLRLT eyes. The RFPD in LLRLT eyes significantly increased 5 minutes after LLRLT and the increment was 1.70±0.83 % (p = 0.0389). The RFPD significantly decreased from 5 minutes to 1 hour after LLRLT with a mean of -2.62±0.86 % decrement (p = 0.0031). The RFPD levels returned to baseline at 1 hour after LLRLT (p = 0.8646). However, compared with insignificant RFPD changes in non-LLRLT eyes, there was no significant difference in RFPD changes at any sampling point. No significant changes in RFT, CFBF, and CFT were found in LLRLT eyes at each sampling point. CONCLUSION: Although LLRLT has no effect on the choroid, it may cause a short-term transient increase in RFPD. It will provide theoretical support for the role of LLRLT in myopia control.

Anti-depression effectiveness of essential oil from the fruits of Zanthoxylum bungeanum maxim. on chronic unpredictable mild stress-induced depression behavior in mice.

The fruits of Zanthoxylum bungeanum Maxim. Was a popular traditional Chinese herbal medicine for pain relief, itching prevention, and diarrhea relief. The fruits of Zanthoxylum bungeanum Maxim. Essential oil (HEO) had an effect of improving anxiety and other emotional disorders. In this paper, we aim to systematically research the antidepressant effects of HEO on Chronic Mild Unpredictable Stimulation (CUMS) mice and explore the relevant molecular mechanisms. Experimental mice were exposed to CUMS for 8 weeks. Meanwhile, for 8 weeks, Sertraline hydrochloride (20 mg/kg/day) and HEO (50, 100, and 150 mg/kg/day) were administered by gavage. HEO treatment increased residence time of central zone in OFT and open-arm in EPM test but decreased immobility times in FST and TST. Moreover, HEO treatment improved the levels of 5-HT, DA, NE, and BDNF, but reduced CRF and CORT levels of the HPA axis in the hippocampus. Network pharmacology predicted the possible mechanisms for the antidepressant effects of HEO by regulation of PI3K/Akt signaling pathway. The mRNA expression of PI3K and Akt were increased, and immunofluorescence results in the hippocampus indicated that HEO treatment could increase the phosphorylation of PI3K and Akt. Besides, the viability of CORT-treated PC12 cells was significantly improved by HEO treatment. The AO-EB staining, MOMP analysis, and flow cytometry analysis results showed HEO inhibiting the CORT-induced apoptosis in PC12 cells significantly. Besides, the phosphorylation of PI3K and Akt in COTR-induced PC12 cells could increase by HEO treatment. In conclusion, HEO ameliorated depression behavior induced by CUMS, potentially via regulating HPA axis and activating PI3K/Akt signaling pathway to reduce neuronal apoptosis.

An Integrated Approach Based on Network Analysis Combined With Experimental Verification Reveals PI3K/Akt/Nrf2 Signaling Is an Important Way for the Anti-Myocardial Ischemia Activity of Yi-Qi-Tong-Luo Capsule.

Background: Yiqi-Tongluo Capsule (YTC) is a Chinese traditional patent medicine that has been used in the treatment of myocardial ischemia (MI). However, its molecular mechanisms against MI have not been clear. Methods: Network analysis and experimental verification were used to explore the potential molecular mechanisms of YTC for MI treatment. Firstly, the main components in the capsules and the potential targets of these components were predicted by online databases. The MI related genes were collected from Genecards and Online Mendelian Inheritance in Man (OMIM) databases. The drug targets and disease targets were intersected, and then the protein-protein interaction (PPI) and Drug-Molecular-Target-Disease Network (DMTD) were constructed, and GO enrichment analysis and KEGG pathway enrichment analysis were performed. Based on the H2O2-stimulated H9c2 cells, flow cytometry, western blot (WB) and immunofluorescence experiments were performed to verify the network analysis prediction. Results: A total of 100 active components and 165 targets of YTC were predicted, in which there were 109 targets intersected with the targets of MI. GO and KEGG analysis showed that these potential targets were related to a variety of biological processes and molecular mechanisms, including oxidative stress and PI3K/AKT pathway. Astragaloside IV (AS IV) and paeoniflorin (PAE) might be the main active components in YTC. The results of cell counting kit-8 (CCK-8) showed that YTC alleviated the damage of H2O2 to H9c2 cells. The results of flow cytometry, DAPI staining and JC-1 probe showed that YTC alleviated H2O2 induced apoptosis in H9c2 cells. In addition, YTC reduced the level of intracellular superoxide anion, increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA) in H2O2-induced H9c2 cells. The results of immunofluorescence and WB showed that the phosphorylation of PI3K and Akt were increased, the expression of Bcl-2 was up-regulated and the expression of cleaved caspase-3 and Bax were down-regulated. Besides, the nuclear translocation of Nrf2 were increased. Conclusion: In conclusion, the results of this study showed that YTC might alleviate MI by suppressing apoptosis induced by oxidative stress via the PI3K/Akt/Nrf2 signal pathway.

Apoptosis Triggering, an Important Way for Natural Products From Herbal Medicines to Treat Pancreatic Cancers.

Pancreatic cancer, a poor prognosis and high morbidity and mortality cancer, is a malignant tumor occurring in pancreatic exocrine glands. Currently, surgery and gemcitabine (Gem) are commonly used to treat pancreatic cancers. However, the high recurrence rate and resistance makes the therapeutic effects still unsatisfied. Apoptosis is comprehensively recognized as one of the major ways of the programmed cell death, refers to the autonomous and orderly death process of cells in order to maintain the stability of the body's environment after receiving a certain signal or stimulation. Currently, it has also been proven to be a promising way for the treatment of pancreatic cancer. Nowadays, some active ingredients from herbal medicine have been reported to be effective for the treatment of pancreatic cancer via inducing cells apoptosis. Therefore, this article reviews the current references regarding anti pancreatic cancer effects of natural products derived from herbal medicines via triggering apoptosis, and summarizes the related potential signal pathways, including death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, MAPK mediated apoptotic pathway, ERS mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other pathways such as JAK-STAT signal pathway, which can lay a certain foundation for the research and development of new natural products against pancreatic cancer.