Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Regulation mechanism and bioactivity characteristic of surfactin homologues with C14 and C15 fatty acid chains.

BACKGROUND: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities. RESULTS: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities. CONCLUSION: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.

The antidepressive mechanism of Longya Lilium combined with Fluoxetine in mice with depression-like behaviors.

Traditional Chinese medicine is one of the most commonly used complementary and alternative medicine therapies for depression. Integrated Chinese-western therapies have been extensively applied in numerous diseases due to their superior efficiency in individual treatment. We used the meta-analysis, network pharmacology, and bioinformatics studies to identify the putative role of Longya Lilium combined with Fluoxetine in depression. Depression-like behaviors were mimicked in mice after exposure to the chronic unpredictable mild stress (CUMS). The underlying potential mechanism of this combination therapy was further explored based on in vitro and in vivo experiments to analyze the expression of COX-2, PGE2, and IL-22, activation of microglial cells, and neuron viability and apoptosis in the hippocampus. The antidepressant effect was noted for the combination of Longya Lilium with Fluoxetine in mice compared to a single treatment. COX-2 was mainly expressed in hippocampal CA1 areas. Longya Lilium combined with Fluoxetine reduced the expression of COX-2 and thus alleviated depression-like behavior and neuroinflammation in mice. A decrease of COX-2 curtailed BV-2 microglial cell activation, inflammation, and neuron apoptosis by blunting the PGE2/IL-22 axis. Therefore, a combination of Longya Lilium with Fluoxetine inactivates the COX-2/PGE2/IL-22 axis, consequently relieving the neuroinflammatory response and the resultant depression.

Porous Titanium Scaffolds with Mechanoelectrical Conversion and Photothermal Function: A Win-Win Strategy for Bone Reconstruction of Tumor-Resected Defects.

Bone metastases severely threaten the lives of patients. Although surgical treatment combined with adjuvant chemotherapy significantly improves the survival rate of patients, tumor recurrence, or metastasis after surgical resection and bone defects caused by surgical treatment remain major challenges for clinicians. Given the abovementioned clinical requirements, barium titanate-containing iron-coated porous titanium alloy scaffolds have been proposed to promote bone defect repair and inhibit tumor recurrence. Fortunately, in vitro and in vivo experimental research confirms that barium titanate containing iron-coated porous titanium alloy scaffolds promote osteogenesis and bone reconstruction in defect repair via mechanoelectric conversion and inhibit tumor recurrence via photothermal effects. Furthermore, the underlying and intricate mechanisms of bone defect repair and tumor recurrence prevention of barium titanate-containing iron-coated porous titanium alloy scaffolds are explored. A win-win strategy for mechanoelectrical conversion and photothermal functionalization provides promising insights into bone reconstruction of tumor-resected defects.

Electroacupuncture inhibits the expression of HMGB1/RAGE and alleviates injury to the primary motor cortex in rats with cerebral ischemia.

Background: The high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) signaling pathway holds promise as a potential therapeutic target for ischemic brain injury. The effects of FPS-ZM1 and electroacupuncture (EA) on activation of the HMGB1/RAGE signaling pathway after cerebral ischemia remain uncertain. Methods: Middle cerebral artery occlusion (MCAO) model was established. Neurological function was assessed using Longa scores. Nissl staining was used to observe the morphology of neurons. The expression levels of HMGB1 and RAGE were assayed with immunofluorescence staining and western blot. Results: The results showed that EA and FPS-ZM1 could reduce the neural function score and neurons cell injury in cerebral ischemia rats by inhibiting the expression of HMGB1 and RAGE in primary motor cortex (M1) region. In addition, EA combined with FPS-ZM1 had a better therapeutic effect. Conclusions: The HMGB1/RAGE pathway could be activated after cerebral ischemia. Both EA and FPS-ZM1 improved neurological deficits and attenuated neuronal damage in rats. They had synergistic effects. These interventions were observed to mitigate brain damage by suppressing the activation of HMGB1/RAGE.

Regulatory Effect of Electroacupuncture on Hypothalamic Serotonin and its Receptor in Rats with Cerebral Ischemia.

BACKGROUND: Previous studies have shown that the neurological damage caused by middle cerebral artery occlusion (MCAO) is not only limited to local infarction but can also cause secondary damage in distant sites, such as the hypothalamus. 5-hydroxytryptamine (5-HT)/ 5-HT transporter (5-HTT) and 5-HT receptor 2A (5-HT2A) are important in the treatment of cerebrovascular diseases. OBJECTIVE: This study aimed to study the effect of electroacupuncture (EA) on the expression of 5- HT, 5-HTT, and 5-HT2A in the hypothalamus of rats with ischemic brain injury and to explore the protective effect and potential mechanism of EA on the secondary injury of cerebral ischemia. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: sham group, model group, and EA group. The permanent middle cerebral artery occlusion (pMCAO) method was used to induce ischemic stroke in rats. In the EA group, the Baihui (GV20) and Zusanli (ST36) points were selected for treatment, which was administered once per day for two consecutive weeks. The neuroprotective effect of EA was evaluated by nerve defect function scores and Nissl staining. The content of 5-HT in hypothalamus was detected by enzyme linked immunosorbent assay (ELISA), and the expression of 5-HTT and 5-HT2A were detected by Western blot. RESULTS: Compared with that in the sham group, the nerve defect function score in the model group rats was significantly increased, the hypothalamus tissue showed obvious nerve damage, the levels of 5-HT and the expression of 5-HTT were significantly reduced, and the expression of 5-HT2A was significantly increased. After 2 weeks of EA treatment, the nerve defect function scores of pMCAO rats were significantly reduced, the hypothalamic nerve injury was significantly reduced, the levels of 5-HT and the expression of 5-HTT were significantly increased, and the expression of 5-HT2A was significantly decreased. CONCLUSION: EA has a certain therapeutic effect on hypothalamic injury secondary to permanent cerebral ischemia, and its potential mechanism may be closely related to the upregulation of 5-HT and 5-HTT expression and the downregulation of 5-HT2A expression.

Moxibustion improves hypothalamus Aqp4 polarization in APP/PS1 mice: Evidence from spatial transcriptomics.

Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic endfeet. Loss of AQP4 polarization is associated with many diseases. In Alzheimer's disease (AD), AQP4 loses its normal location and thus reduces the clearance of amyloid-ß plaques and tau protein. Clinical and experimental studies showed that moxibustion can improve the learning and memory abilities of AD. To explore whether moxibustion can affect the polarization of AQP4 around the blood-brain barrier (BBB), we used spatial transcriptomics (ST) to analyze the expression and polarization of Aqp4 in wild-type mice, APP/PS1 mice, and APP/PS1 mice intervened by moxibustion. The results showed that moxibustion improved the loss of abnormal polarization of AQP4 in APP/PS1 mice, especially in the hypothalamic BBB. Besides, the other 31 genes with Aqp4 as the core have similar depolarization in APP/PS1 mice, most of which are also membrane proteins. The majority of them have been reversed by moxibustion. At the same time, we employed the cerebrospinal fluid circulation gene set, which was found to be at a higher level in the group of APP/PS1 mice with moxibustion treatment. Finally, to further explore its mechanism, we analyzed the mitochondrial respiratory chain complex enzymes closely related to energy metabolism and found that moxibustion can significantly increase the expression of mitochondrial respiratory chain enzymes such as Cox6a2 in the hypothalamus, which could provide energy for mRNA transport. Our research shows that increasing the polarization of hypothalamic Aqp4 through mitochondrial energy supply may be an important target for moxibustion to improve cognitive impairment in APP/PS1 mice.

Spatial transcriptomics shows moxibustion promotes hippocampus astrocyte and neuron interaction.

AIMS: Alzheimer's disease (AD) is a common and irreversible neurodegenerative disease accompanied by extensive synaptic loss. Previous studies found that moxibustion had good therapeutic effects on AD. We here investigated whether moxibustion could alleviate the cognitive impairment of AD by promoting the "astrocyte-neuron" interaction and enhancing synaptic plasticity. MATERIALS AND METHODS: Moxibustion treatment was administrated to Baihui (GV20) and Yongquan (KI1) in APP/PS1 mice. We first evaluated the behavior of APP/PS1 mice with Morris water maze test, and observed the synaptic structure before and after moxibustion intervention. Then, the transcriptome characteristics (TC) and "astrocyte-neuron" interaction were evaluated by spatial transcriptomics (ST). CD38 and its ligand Pecam1, one of the energy shuttle pathways between neurons and astrocytes, were also be detected. KEY FINDINGS: The results supported that moxibustion increased learning and memory ability and synaptic structure. ST showed that the TC were more similar between the moxibustion and control groups. Moxibustion enhanced the number of ligand - receptor pairs between astrocytes and neurons. And the score of interaction intensity and the proportion of interaction were also increased. Meanwhile, the energy of astrocytes and neurons was significantly altered. Additionally, moxibustion could significantly improve the function of CD38 and its ligand Pecam1 which were previously reported having the function of transporting mitochondria from astrocytes to neurons, and then providing energy for neurons. SIGNIFICANCE: Our study provides new evidences for the use of moxibustion to increase the "astrocyte - neuron" interaction thus to enhance synaptic plasticity of APP/PS1 mice.

Fuzi-Lizhong Decoction Alleviates Nonalcoholic Fatty Liver Disease by Blocking TLR4/MyD88/TRAF6 Signaling.

Background: Fuzi-Lizhong decoction (FLD) derives from the ancient Chinese Pharmacopoeia and has been clinically used for years. The present study aimed to investigate the activities and underlying mechanisms of FLD against nonalcoholic fatty liver disease (NAFLD). Methods: In vivo studies were conducted by inducing NAFLD in rats with a high-fat diet, and in vitro studies were performed on HL-7702 cells treated with oleic and linoleic acids. Total cholesterol (TC), triglyceride (TG), and blood glucose (Glu) levels were detected using an automatic biochemical analyzer. The expression of IL-2, IL-6, and TNF-α in sera and cell culture supernatants was measured by ELISA. The mRNA and protein levels of TLR4, MyD88, and TRAF6 were measured in liver tissue and HL-7702 cells using reverse transcription-quantitative polymerase chain reaction and western blot. Results: FLD significantly reduced the TC, TG, Glu, FFA, IL-2, IL-6, and TNF-α levels in NAFLD rats and HL-7702 cells. Analysis of liver lipid content by Oil Red O staining revealed a significant increase in hepatic lipid accumulation in rats with NAFLD, but this lipid accumulation was reversed by FLD treatment. In addition, the mRNA expression levels of TLR4, MyD88, TRAF6, and NF-κB p65 as well as the protein levels of TLR4, MyD88, TRAF6, and NF-κB p65 were decreased after FLD treatment. FLD significantly reduced inflammation and improved collagen accumulation in vivo and in vitro by inhibiting the activation of the TLR4/MyD88/TRAF6 signaling pathway. Conclusions: FLD exerted potent protective effects against NAFLD via TLR4/MyD88/TRAF6 signaling. These findings provide novel insights into the mechanisms whereby this compound acts as an anti-inflammatory agent and highlight the potential application of FLD in the treatment of acute liver failure (ALF).

Current Research on Complementary and Alternative Medicine in the Treatment of Premature Ovarian Failure: An Update Review.

Complementary and alternative medicine (CAM) encompasses a wide range of different non-mainstream therapies that have been increasingly used for the treatment or adjunct treatment of various ailments, with premature ovarian failure (POF) being one of the most common conditions treated with CAM. This review updates the progress of CAM in the treatment of POF, and we focus specifically on reviewing the evidence for the efficacy and mechanisms of a range of CAM treatments in POF, including single herbal medicines and their active ingredients, compound Chinese medicines, acupuncture and moxibustion, psychotherapy, exercise, vitamins, massage, and dietary supplements. According to the literature, CAM is very helpful for improving POF symptoms, and we hope to provide some instructive suggestions for clinical treatment and experimental research in the future. However, more clinical trials are needed to prove the safety of CAM.

The Impact of Zinc Supplementation on Critically Ill Patients With Acute Kidney Injury: A Propensity Score Matching Analysis.

Background: Zinc is an essential trace element involved in multiple metabolic processes. Acute kidney injury (AKI) is associated with low plasma zinc, but outcomes with zinc supplementation in critically ill patients with AKI remain unknown. Our objective was to investigate the effectiveness of zinc supplementation in this patient population. Methods: Critically ill patients with AKI were identified from the Medical Informative Mart for Intensive Care IV database. Prosperity score matching (PSM) was applied to match patients receiving zinc treatment to those without zinc treatment. The association between zinc sulfate use and in-hospital mortality and 30-day mortality, need for renal replacement therapy (RRT), and length of stay was determined by logistic regression and Cox proportional hazards modeling. Results: A total of 9,811 AKI patients were included in the study. PSM yielded 222 pairs of patients who received zinc treatment and those who did not. Zinc supplementation was associated with reduced in-hospital mortality (HR = 0.48 (95% CI: 0.28, 0.83) P = 0.009) and 30-day mortality (HR = 0.51 (95% CI, 0.30, 0.86) P = 0.012). In the subgroup analysis, zinc use was associated with reduced in-hospital mortality in patients with stage 1 AKI and those with sepsis. Conclusions: Zinc supplementation was associated with improved survival in critically ill patients with AKI. The supplementation was especially effective in those with stage 1 AKI and sepsis. These results need to be verified in randomized controlled trials.

The Effects of Moxibustion on Learning and Memory and m6A RNA Methylation in APP/PS1 Mice.

Objectives: To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products Aß and Tau protein via decreasing N6-methyladenosine (m6A). Methods: APP/PS1 mice were randomly divided into model group (APP/PS1) and moxibustion group (APP/PS1+Mox). C57BL/6J mice were used as a control group (Control). Learning and memory abilities were assessed by the Morris water maze. Aß, Tau, phosphorylated Tau (p-Tau), and YTHDF1 proteins were detected in the mouse cortex and hippocampus by immunofluorescence and western blot. Altered m6A expression levels in hippocampal and cortical tissues were measured with the m6A RNA methylation quantification assay kit. RNA transcript levels of YTHDF1, METTL3, and FTO in the hippocampus and cortex were measured by q-PCR. Results: Moxibustion shortened the escape latency, increased the number of platform crossings, and increased the percentage of swimming time in the target quadrant of APP/PS1 mice. Meanwhile, moxibustion reduced the levels of Aß, Tau, and p-Tau proteins both in the hippocampal and cortical regions of APP/PS1 mice. In addition, the total amount of m6A in the hippocampal and cortical regions of APP/PS1 mice was significantly reduced after moxibustion. The expression of YTHDF1 in the hippocampal region of APP/PS1 mice increased and that in the cortical region decreased after moxibustion treatment. Conclusion: Moxibustion improves the learning and memory abilities and reduces the deposition of Aß and Tau protein pathological products in APP/PS1 mice. This may be related to the fact that moxibustion reduces the total amount of m6A and inhibits its binding enzyme YTHDF1 in the hippocampus and cortex of APP/PS1 mice.

Xiaoyao Powder in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide with alarming prevalence. Due to its complex pathogeneses and considerable individual heterogeneity in disease, there is no specific medication to NAFLD safely and effectively. Therefore, there is a great need to explore complementary and alternative therapies. Xiaoyao Powder (XYP), a classic Chinese formula, has been tremendously applied to gastrointestinal diseases, especially non-alcoholic fatty liver disease. However, the efficacy and safety of XYP have not been fully assessed. AIM OF THE STUDY: To assess the effectiveness and safety of XYP for NAFLD. MATERIALS AND METHODS: The assigned registration number on the PROSPERO platform of this meta-analysis is CRD42020192154, and we strictly followed the protocol. We searched eight primary databases from their inception to June 2020. Two authors independently identified random controlled trials (RCTs) of XYP for NAFLD and evaluated the quality of the retrieved articles by Cochrane accessing risk bias tool. At least one of the following indices was thoroughly documented for outcome measurement: total effective rate, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), body mass index (BMI), and adiponectin. We calculated risk ratio (RR) and mean difference (MD) for dichotomous data and continuous variables with a 95% confidence interval (CI). R 4.0.5 software was employed for data synthesis. RESULTS: Consequently, we identified 12 studies with 1012 participants. XYP, whether individually or combined with essential treatment, ameliorated NAFLD regardless of the course of the disease or curative duration. This benefit was mainly driven by regulating levels of serum markers, involving TC, TG, ALT, AST, GGT, and adiponectin. Three studies where statins were concerned about drug safety reported several adverse events with clinical symptoms, varying from flatulence, constipation, and diarrhea to rash, whereas others did not. CONCLUSION: Our findings provided evidence that XYP is a therapeutic option to treat NAFLD effectively and safely. Notwithstanding, a precise and comprehensive conclusion calls for RCTs on a larger scale with more rigorous designs considering the inferior methodological quality and limited retrieved articles.

Simultaneous detection of ten kinds of insecticide residues in honey and pollen using UPLC-MS/MS with graphene and carbon nanotubes as adsorption and purification materials.

An analytical method of simultaneous detection of ten insecticide residues in honey and pollen was established. The samples were purified with QuEChERS approach using new adsorbents and analyzed with UPLC-MS/MS. The results showed that both of graphene and carbon nanotubes were highly efficient adsorbents for the dSPE clean up to eliminate coextractives in the samples, and graphene was superior to carbon nanotubes for the detection of pesticide residues in honey and pollen samples. The proposed method was used to detect pesticide residues in 25 honey samples and 30 pollen samples which were randomly collected from more than ten provinces in China. All honey samples contain 1-27 µg/kg of chlorpyrifos residues. Only 4% of the honey samples were detected containing acetamiprid and imidacloprid, while the other seven pesticides were not detected. Chlorpyrifos residues were found in all pollen samples (5-66 µg/kg), among which twenty percent exceeded the maximum residue limits (MRLs, 50 µg/kg, European Commission Regulation). Most of the pollen samples containing pesticide concentrations higher than MRLs were collected from rape, followed by lotus, camellia, and rose. Besides, 36.7% and 33.3% of the pollen samples had imidacloprid and flupyradifurone higher than 5 µg/kg. A total of 26.7% pollen samples were detected containing bifenthrin, while none of the other six pesticides were detected in pollen samples.

Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1ß, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD. Methods: Twenty male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aß1 - 42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint "Baihui" (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR). Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6). Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.

New Internet-Based Warfarin Anticoagulation Management Approach After Mechanical Heart Valve Replacement: Prospective, Multicenter, Randomized Controlled Trial.

BACKGROUND: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. OBJECTIVE: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. METHODS: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. RESULTS: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). CONCLUSIONS: The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-032949.

[Evidence mapping of clinical research on 28 Chinese patent medicines for tension-type headache].

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.

Sijunzi, Lizhong, and Fuzilizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease through Activation of PPAR Pathway.

OBJECTIVE: Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD and were thereafter administered Sijunzi (8 g/kg/d), Lizhong (10 g/kg/d), or Fuzilizhong (10 g/kg/d) by gavage for four weeks. Hepatic damage, lipid accumulation, inflammation, autophagy, and peroxisome proliferator-activated receptor-α signaling were evaluated. RESULTS: The high-fat diet-fed rats showed typical symptoms of NAFLD, including elevated levels of hepatic damage indicators, increased hepatic lipid deposition and fibrosis, severe liver inflammation, and prominent autophagy. Upon administration of Sijunzi, Lizhong, and Fuzilizhong, liver health was improved remarkably, along with ameliorated symptoms of NAFLD. In addition, NAFLD-suppressed peroxisome proliferator-activated receptor-α signaling was reactivated after treatment with the three types of decoctions. CONCLUSIONS: The results collectively signify the effective therapeutic and protective functions of Sijunzi, Lizhong, and Fuzilizhong against NAFLD and demonstrate the potential of Chinese herbal medication in mitigating the symptoms of liver diseases. Novelty of the Work. Traditional Chinese herbal medicine has been used for centuries to treat various diseases, but the molecular mechanisms of individual ingredients have rarely been studied. The novelty of our work lies in elucidating the specific signaling pathways involved in the control of NAFLD using three common Chinese herbal decoctions. We suggest that natural herbal formulations can be effective therapeutic agents to combat against NAFLD.

Protective Effect of Fuzi Lizhong Decoction against Non-alcoholic Fatty Liver Disease via Anti-inflammatory Response through Regulating p53 and PPARG Signaling.

Fuzi Lizhong decoction (FLD) is derived from an ancient Chinese Pharmacopoeia and has been used in clinical treatment for years. The present study aimed to investigate the activities and underlying mechanisms of FLD against non-alcoholic fatty liver disease (NAFLD). Network pharmacology analysis demonstrated that FLD might affect NAFLD through regulating p53 and peroxisome proliferator activated receptor gamma (PPARG), which has been confirmed in vitro and in vivo. In vivo NAFLD was induced in rats by a high-fat diet, and in vitro studies were performed on HL-7702 cells treated with oleic acid and linoleic acid. We showed that FLD significantly improved NAFLD by regulating the immune system to induce the release of interleukin-10 (IL-10), interferon-α (IFN-α), and IFN-ß through activating p53 signaling and inhibiting PPARG signaling in vivo and in vitro. P53 inhibition induced by NAFLD was recused by FLD, while PPARG overexpression induced by NAFLD was inhibited by FLD. In addition, NAFLD resulted in increased levels of total cholesterol, triglyceride, and blood glucose in the serum and free fatty acid in the liver, which were reduced by FLD treatment. Evidently, FLD exhibited potent protective effects against NAFLD via p53 and PPARG signaling. Our study could provide novel insights into the mechanisms of FLD as an anti-inflammatory candidate for the treatment of NAFLD in the future.

Study on the clinical assessment of integrated rehabilitation of Traditional Chinese Medicine and western medication for acute myocardial infarction.

OBJECTIVE: This trial aims to evaluate the efficacy and safety of the Baduanjin exercise in patients with acute myocardial infarction (AMI). METHODS: A single-center, open, randomized controlled clinical trial will be conducted to evaluate the effectiveness of the Baduanjin exercise on the rehabilitation of AMI patients. It plans to enroll 64 patients. Patients will be divided evenly into 2 groups using a random number table method. There will be 32 cases in each group. Patients in the experimental group will be treated with standardized drug therapy combined with Baduanjin exercise, while patients in the control group will be treated with standardized drug therapy combined with routine exercise. The primary outcome is the peak oxygen consumption (Peak VO2) during cardiopulmonary exercise test (CPET). The secondary outcomes include CPET, echocardiography, Seattle angina pectoris scale, hospital depression and anxiety scale, Pittsburgh Sleep Quality Index scale, scores of 4 examinations, and diagnostic methods of traditional Chinese medicine and composite endpoint events, etc. DISCUSSION:: This study will be the first to evaluate the effect of the Baduanjin exercise on the Peak VO2 in patients with AMI. STUDY REGISTRATION: This study has been registered on the Chinese Clinical Trial Registry (No: ChiCTR1800016209, protocol version 1.2).