Dual role of Nrf2/HO-1 pathway in Z-ligustilide-induced ferroptosis against AML cells.

BACKGROUND: The scarcity of drugs targeting AML cells poses a significant challenge in AML management. Z-Ligustilide (Z-LIG), a phthalide compound, shows promising pharmacological potential as a candidate for AML therapy. However, its precise selective mechanism remains unclear. PURPOSE: In order to assess the selective inducement effects of Z-LIG on ferroptosis in AML cells and explore the possible involvement of the Nrf2/HO-1 pathway in the regulation of ferroptosis. METHODS: Through in vitro cell proliferation and in vivo tumor growth tests, the evaluation of Z-LIG's anticancer activity was conducted. Ferroptosis was determined by the measurement of ROS and lipid peroxide levels using flow cytometry, as well as the observation of mitochondrial morphology. To analyze the iron-related factors, western blot analysis was employed. The up-regulation of the Nrf2/HO-1 axis was confirmed through various experimental techniques, including CRISPR/Cas9 gene knockout, fluorescent probe staining, and flow cytometry. The efficacy of Z-LIG in inducing ferroptosis was further validated in a xenograft nude mouse model. RESULTS: Our study revealed that Z-LIG specifically triggered lipid peroxidation-driven cell death in AML cells. Z-LIG downregulated the total protein and nuclear entrance levels of IRP2, resulting in upregulation of FTH1 and downregulation of TFR1. Z-LIG significantly increased the susceptibility to ferroptosis by upregulating ACSL4 levels and simultaneously suppressing the activity of GPX4. Notably, the Nrf2/HO-1 pathway displayed a twofold impact in the ferroptosis induced by Z-LIG. Mild activation suppressed ferroptosis, while excessive activation promoted it, mainly driven by ROS-induced labile iron pool (LIP) accumulation in AML cells, which was not observed in normal human cells. Additionally, Nrf2 knockout and HO-1 knockdown reversed iron imbalance and mitochondrial damage induced by Z-LIG in HL-60 cells. Z-LIG effectively inhibited the growth of AML xenografts in mice, and Nrf2 knockout partially weakened its antitumor effect by inhibiting ferroptosis. CONCLUSION: Our study presents biological proof indicating that the selective initiation of ferroptosis in leukemia cells is credited to the excessive activation of the Nrf2/HO-1 pathway triggered by Z-LIG.

Light/glutathione-ignited nanobombs integrating azo and tetrasulfide bonds for multimodal therapy of colorectal cancer.

Reactive chemical bonds are associated with the generation of therapeutic radicals and gases under internal-external stimuli, which are highly attractive for cancer treatments. However, designing multifunctional nanostructures that incorporate multiple chemical bonds remains a significant challenge. Herein, novel core-shell nanobombs integrating azo (NN) and tetrasulfide bonds (SSSS) have been constructed with sensitive ignition by both near-infrared (NIR) laser and tumor microenvironments (TME) for treating colorectal tumors. The nanobombs (GNR/AIPH@MON@PVP, GAMP) were prepared by the in-situ growth of tetrasulfide-contained mesoporous organosilica nanoshell (MON) on gold nanorods (GNR) as the photothermal initiator, the load of azo compound (AIPH) as the radical producer and polymer modification. Upon NIR irradiation, the GNR core exhibits stable and high photothermal effects because of the passivation of the MON shell, leading to the thermal ablation of cancer cells. Simultaneously, the local hyperthermia ignites AIPH to release alkyl radicals to cause extensive oxidative stress without oxygen dependence. Moreover, the MON shell can be gradually decomposed in a reduced environment and release therapeutic H2S gas because of the cleavage of SSSS bonds by the glutathione (GSH) overexpressed in TME, causing mitochondrial injury. Owing to multifunctional functions, the GAMP significantly inhibits the growth rate of tumors upon NIR irradiation and achieves the highest efficacy among treatments. Therefore, this study presents activatable nanoagents containing multiple chemical bonds and provides insights into developing comprehensive antitumor strategies.

The Efficacy and Safety of Bionic Tiger Bone Powder for the Treatment of Knee Osteoarthritis in Early Stage: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

Objective: This study evaluated the efficacy and safety of bionic tiger bone powder (Jintiange) in comparison to placebo in treating knee osteoarthritis osteoporosis. Methods: A total of 248 patients were randomly allocated to a Jintiange group or a placebo group, undergoing 48 weeks of double-blind treatment. The Lequesne index, clinical symptoms, safety index (adverse events), and Patient's Global Impression of Change score were recorded at pre-determined time intervals. All P values ≤ .05 were deemed statistically significant. Results: Both groups showed a decreasing trend in the Lequesne index, with the Jintiange group's reduction significantly larger from the 12th week (P ≤ .01). Similarly, the effective rate of Lequesne score in the Jintiange group was significantly higher (P < .001). After 48 weeks, clinical symptom score differences between the Jintiange group (2.46 ± 1.74) and the placebo group (1.51 ± 1.73) were statistically significant (P < .05), as were differences in the Patient's Global Impression of Change score (P < .05). Adverse drug reactions were minimal with no significant difference between the groups (P > .05). Conclusion: Jintiange demonstrated superior efficacy over placebo in treating knee osteoporosis, with comparable safety profiles. Findings warrant further comprehensive real-world studies.

Construction of PEGylated chlorin e6@CuS-Pt theranostic nanoplatforms for nanozymes-enhanced photodynamic-photothermal therapy.

Multifunctional nanoagents with photodynamic therapy (PDT) and photothermal therapy (PTT) functions have shown great promise for cancer treatment, while the design and synthesis of efficient nanoagents remain a challenge. To realize nanozyme-enhanced PDT-PTT combined therapy, herein we have synthesized the Ce6@CuS-Pt/PEG nanoplatforms as a model of efficient nanoagents. Hollow CuS nanospheres with an average diameter of âˆ¼ 200 nm are first synthesized through vulcanization using Cu2O as the precursor. Subsequently, CuS nanospheres are surface-decorated with Pt nanoparticles (NPs) as nanozyme via an in-situ reduction route, followed by modifying the DSPE-PEG5000 and loading the photosensitizer Chlorin e6 (Ce6). The obtained Ce6@CuS-Pt/PEG NPs exhibit high photothermal conversion efficiency (43.08%), good singlet oxygen (1O2) generation ability, and good physiological stability. In addition, Ce6@CuS-Pt/PEG NPs show good catalytic performance due to the presence of Pt nanozyme, which can effectively convert H2O2 to O2 and significantly enhance the production of cytotoxic 1O2. When Ce6@CuS-Pt/PEG NPs dispersion is injected into mice, the tumors can be wholly suppressed owing to nanozyme-enhanced PDT-PTT combined therapy, providing better therapeutic effects compared to single-mode phototherapy. Thus, the present Ce6@CuS-Pt/PEG NPs can act as an efficient multifunctional nanoplatform for tumor therapy.

Design and synthesis of cancer-cell-membrane-camouflaged hemoporfin-Cu9S8 nanoagents for homotypic tumor-targeted photothermal-sonodynamic therapy.

Multimodal therapies have aroused great interest in tumor therapy due to their highly effective antitumor effect. However, immune clearance limits the practical application of nanoagents-based multimodal therapies. To solve this problem, we have designed hemoporfin-Cu9S8 hollow nanospheres camouflaged with the CT26 cell membrane (CCM) as a model of multifunctional agents, achieving homologous-targeted synergistic photothermal therapy (PTT) and sonodynamic therapy (SDT). Hollow Cu9S8 as photothermal agents and carriers have been obtained through sulfurizing cuprous oxide (Cu2O) nanoparticles through "Kirkendall effect", and they exhibit hollow nanospheres structure with a size of ∼200 nm. Then, Cu9S8 nanospheres could be used to load with hemoporfin sonosensitizers, and then hemoporfin-Cu9S8 nanospheres (abbreviated as H-Cu9S8) can be further surface-camouflaged with CCM. H-Cu9S8@CCM nanospheres exhibit a broad photoabsorption in the range of 700-1100 nm and high photothermal conversion efficiency of 39.8% under 1064 nm laser irradiation for subsequent PTT. In addition, under the excitation of ultrasound, the loaded hemoporfin could generate 1O2 for subsequent SDT. Especially, H-Cu9S8@CCM NPs are featured with biocompatibility and homologous targeting capacity. When intravenously (i.v.) injected into mice, H-Cu9S8@CCM NPs display a higher blood circulation half-life (3.17 h, 6.47 times) and tumor accumulation amount (18.75% ID/g, 1.94 times), compared to H-Cu9S8 NPs (0.49 h, 9.68% ID/g) without CCM. In addition, upon 1064 nm laser and ultrasound irradiation, H-Cu9S8@CCM NPs can inhibit tumor growth more efficiently due to high accumulation efficiency and synergistic PTT-SDT functions. Therefore, the present study provides some insight into the design of multifunctional efficient agents for homotypic tumor-targeted therapy.

The formation of starch-lipid complexes in instant rice noodles incorporated with different fatty acids: Effect on the structure, in vitro enzymatic digestibility and retrogradation properties during storage.

The formation of starch-lipid complexes in instant rice noodles (IRN) free from and incorporated with fatty acids (FAs) and their impacts on textural, in vitro digestive and retrogradation properties were investigated. The gelatinization enthalpy values of IRN samples (1.24-4.93 J/g) were noticeably decreased (P < 0.05) compared to rice starch samples (2.54-6.89 J/g) fortified with FAs. Additionally, long-chain saturated FAs (stearic acid (SA, C18:0)) complexes produced higher ordered structures than the shorter-chain FAs (C12:0-C16:0), for 18-carbon FAs, the unsaturated FAs (linoleic acid (LOA, C18:2)) exhibited the strongest intermolecular interactions with rice starch. The relative crystallinity of IRN (27.01%-38.47%) was lower than the rice starch-FAs complexes (38.36%-56.80%). FAs delayed the retrogradation degree of IRN storaged at 4 °C for 21 days ascribed to the formation of V-type complexes. Higher enzymatic resistance was observed in IRN added FAs with resistant starch content increased from 5.13% to 14.42% (LOA), and the sample fortified with SA exhibited the highest slowly digestible starch content (35.92%). SEM revealed that the IRN compounded with palmitic acid, SA and LOA displayed more compact and regular structures. Overall, the formation of starch-FAs complexes probably is a novel strategy in improving the textural, digestive, and retrogradation properties of IRN.

The efficacy and safety of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke: systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.

Nanoscale Hf-hematoporphyrin frameworks for synergetic sonodynamic/radiation therapy of deep-seated tumors.

Most of tumors are located in deep-depth of animals, and the therapy of deep-seated tumors remains a severe challenge due to the performance reduction of promising technologies including phototherapy. To solve the problem, herein we have developed a hafnium-hemoporfin frameworks (HfHFs) as multifunctional theranostic nanoplatforms for synergetic sonodynamic therapy (SDT) and radiation therapy (RT) of deep-seated tumors. HfHFs are constructed by a sonication-assisted assembly route with hematoporphyrin monomethyl ether (HMME) sonosensitizer molecules as bridging linkers and Hf4+ as metal nodes. The resulting HfHFs sample is composed of spherical nanoparticles with size of 90-130 nm, and then surface-modified with DSPE-PEG to improve the water-dispersity. Under ultrasound (US) irradiation, HMME ligands in HfHFs can be motivated to produce singlet oxygen (1O2) due to sonodynamic effect. When the HfHFs sample is exposed by X-ray, the high atomic-number Hf4+ in the HfHFs can effectively absorb X-ray to increase RT effect by producing hydroxyl radicals (•OH). When HfHFs dispersion is intravenously injected in the tumor-bearing mice, the tumor can be monitored by CT imaging. Moreover, the deep-seated tumors coated by tissue barriers can be suppressed effectively by the synergistic SDT and RT, which is better than that of SDT or RT alone. Therefore, HfHFs can be employed as a novel nanoagent for the SDT-RT of deep-seated tumors.

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression.

Background: Paeoniflorin (PF) represents the major bioactive constituent of the traditional Chinese medicine plant Paeonia suffruticosa (Ranunculaceae), which has a long history as a folk medicine in Asian. Paeoniflorin, a bitter pinene monoterpene glycoside, has antidepressant effects, but its potential therapeutic mechanism has not been thoroughly explored. Methods: Experimental depression in rats was established by the chronic unpredictable mild stress (CUMS) combined with orphan method, and the efficacy of paeoniflorin on depression was evaluated by the sucrose preference test and open field test. The antidepressant mechanism of paeoniflorin was investigated by metabolomic and network pharmacology. The relevant pathways of biomarkers highlighted in metabolomics were explored, and the possible targets of paeoniflorin in the treatment of depression were further revealed through network analysis. The binding activity of paeoniflorin to key targets was verified by molecular docking. Results: Metabolomics showed that rats with CUMS-induced depression had urine metabolic disorders, which were reversed by paeoniflorin through the regulation of metabolic pathways. Metabolites that play a key role in the function of paeoniflorin include citric acid, thiamine monophosphate, gluconolactone, 5-hydroxyindoleacetic acid and stachyose. Key predicted targets are SLC6A4, TNF, IL6 and SLC6A3. An important metabolic pathway is the Citrate cycle (TCA cycle). Conclusion: Network integrative analysis in this study showed that paeoniflorin could improve depressive-like symptoms in model rats with CUMS-induced depression and overall correct the disordered metabolic profile through multiple metabolic pathways.

Multifunctional Doxorubicin@Hollow-Cu9S8 nanoplatforms for Photothermally-Augmented Chemodynamic-Chemo therapy.

Multimodal therapy has attracted increasing interests in tumor treatment due to its high anti-cancer efficacy, and the key is to develop multifunctional nanoagents. The classic multifunctional nanoagents are made up of expensive and complex components, leading to limited practical applications. To solve these problems, we have developed the polyethylene glycol (PEG) coated hollow Cu9S8 nanoparticles (H-Cu9S8/PEG NPs), whose H-Cu9S8 component exhibits the photothermal effect for near-infrared (NIR) photothermal therapy (PTT), the Fenton-like catalytic activity for chemodynamic therapy (CDT), and the drug-loading capacity for chemotherapy. The H-Cu9S8/PEG NPs with a diameter of âˆ¼ 100 nm have been synthesized by sulfurizing cuprous oxide (Cu2O) nanoparticles through "Kirkendall effect", and they exhibit high photothermal conversion efficiency of 40.9%. Meanwhile, the H-Cu9S8/PEG NPs are capable of a Fenton-like reaction, which can be augmented by 2 times under the NIR irradiation. The hollow structure gives the H-Cu9S8/PEG high doxorubicin (DOX) loading capacity (21.1%), and then the DOX release can be further improved by pH and photothermal effect. When the DOX@H-Cu9S8/PEG dispersions are injected into the tumor-bearing mice, the tumor growth can be efficiently inhibited due to the synergistic effect of photothermally-augmented CDT-chemo therapy. Therefore, the DOX@H-Cu9S8/PEG can serve as a multifunctional nanoplatform for photothermally-augmented CDT-chemo treatment of malignant tumors.

The mechanism study of Miao medicine Tongfengting decoction in the treatment of gout based on network pharmacology and molecular docking.

AIM: This study sought to clarify the mechanism of action of Miao medicine Tongfengting decoction in the treatment of gout through network pharmacology and molecular docking by searching for its key targets and related pathways. METHODS: The active ingredients of Miao medicine Tongfengting Decoction were obtained from the TCMSP data platform, searched the relevant databases for gout-related targets,using String and Cytoscape 3.9 to build a "compound-cross-target-disease" network diagram,performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis in the DAVID database, and performed the docking analysis using PyMoL 2.3.0 and AutoDock. RESULTS: After screening, 298 main targets of the Miao medicine Tongfengting decoction for gout were identified. The target network is established, and the topology of protein-protein interaction (PPI) network is analyzed. The enrichment analysis of KEGG pathway showed that these targets were related to Pathways in cancer, PI3K Akt signaling pathway, MAPK signaling pathway and other pathways. Molecular docking showed that the target protein had good binding power with the main active components of the compound of Miao medicine Tongfengting Decoction. CONCLUSION: Miao medicine Tongfengting decoction probably regulates immune mechanism using a multi-component, multi-target, and multi-pathway strategy to reduce inflammatory response and exert its therapeutic effect on gout.

Transforming a Sword into a Knife: Persistent Phototoxicity Inhibition and Alternative Therapeutical Activation of Highly-Photosensitive Phytochlorin.

The phototoxicity of photosensitizers (PSs) is a double-edged sword with one edge beneficial for destroying tumors while the other is detrimental to normal tissues, and the conventional "OFF-ON" strategy provides temporary inhibition so that phototoxicity would come sooner or later due to the inevitable retention and transformation of PSs in vivo. We herein put forward a strategy to convert "double-edged sword" PSs into "single-edged knife" ones with simultaneously persistent phototoxicity inhibition and alternative multiple therapeutical activation. The Chlorin e6 (Ce6) as the PS model directly assembles with Cu2+ ions into nanoscale frameworks (nFs) whose Cu2+-coordination includes both carboxyl groups and a porphyrin ring of Ce6 instead of Fe3+/Mn2+-coordination with only carboxyl groups. Compared to the high phototoxicity of Ce6, the nFs exhibit efficient energy transfer due to the dual-coordination of paramagnetic Cu2+ ions and the aggregation, achieving the persistent and high phototoxicity inhibition rate of >92%. Alternatively, the nFs not only activate a high photoacoustic contrast and near-infrared (NIR)-driven photothermal efficacy (3.5-fold that of free Ce6) due to the aggregation-enhanced nonradiative transition but also initiate tumor microenvironment modulation, structure disassembly, and chemodynamic effect by Cu2+ ions. Given these merits, the nFs achieve long-term biosecurity, no retina injury under sunlight, and a higher therapeutical output than the photodynamic effect of Ce6. This work presents a possibility of converting numerous highly phototoxic porphyrins into safe and efficient ones.

Ferroptosis as a New Mechanism in Parkinson's Disease Therapy Using Traditional Chinese Medicine.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, among medications used to treat PD, only levodopa exhibits a limited disease-modifying effect on early-onset PD, but it cannot delay the progression of the disease. In 2018, for the first time, the World Health Organization included traditional Chinese medicine (TCM) in its influential global medical compendium. The use of TCM in the treatment of PD has a long history. At present, TCM can help treat and prevent PD. Iron metabolism is closely associated with PD. Ferroptosis, which is characterized by the accumulation of lipid peroxides, is a recently discovered form of iron-dependent cell death. The research literature indicates that ferroptosis in dopaminergic neurons is an important pathogenetic mechanism of PD. TCM may thus play unique roles in the treatment of PD and provide new ideas for the treatment of PD by regulating pathways associated with ferroptosis.

Synthesis of one-for-all type Cu5FeS4 nanocrystals with improved near infrared photothermal and Fenton effects for simultaneous imaging and therapy of tumor.

CuS materials exhibit excellent near infrared (NIR) photoabsorption and photothermal effect, but they are lack of magnetic resonance imaging (MRI) ability. Fe-based nanomaterials possess MRI capacity, but they usually exhibit poor NIR photoabsorption. In order to solve the above problems, we synthesize three kinds of CuxFeySz samples, including FeS2, CuFeS2 and Cu5FeS4 nanomaterials. With the Cu/Fe ratios increase from 0/1.0 to 1.0/1.0 and 5.0/1.0, the localized surface plasmon resonances (LSPRs) characteristic peaks shift to longer wavelength, and the photothermal transduction efficiencies go up from 24.4% to 36.6% and 45.9%. Thus, Cu5FeS4 is found to be the most excellent sample. Especially, Cu5FeS4 exhibits photothermal-enhanced Fenton effect, which can produce hydroxyl radical (·OH) under a wide pH range (e.g., pH = 5.4-7.4) to realize the chemodynamic effect. In addition, Cu5FeS4 can be employed as an efficient MRI contrast agent. When Cu5FeS4 dispersion is intravenously injected into the mouse, the tumor can be detected by MRI as well as thermal imaging, and eliminated through photothermal-enhanced chemodynamic effect. Therefore, Cu5FeS4 can be used as an efficient "one-for-all" type agent for MRI-guided photothermal-enhanced chemodynamic therapy of tumor.

Cell membrane camouflaged bismuth nanoparticles for targeted photothermal therapy of homotypic tumors.

Bi nanoparticles (NPs) have been demonstrated as effective all-in-one type theranostic agent for imaging-guided photothermal therapy, but their applications have been limited by relatively low biocompatibility and target accumulation capacity. To address this issue, we report the camouflage of Bi NPs (size: ~42 ± 2 nm) by using the mouse colon cancer CT26 cells membrane (CT26 CCM). The camouflaging process confers the efficient coating of CCM shell layer with thickness of ~8 ± 2 nm on Bi NPs cores, which can be confirmed by TEM image, zeta potential and protein gel electrophoresis tests. Simultaneously, CCM shell has no side effects on the photoabsorption/photothermal effect. Importantly, Bi@CCM NPs retain significant features of CCM, including good biocompatibility and homologous targeting ability. When Bi@CCM dispersion was intravenously (i.v.) injected into mice, they exhibited higher blood circulation half-life (11.5 h, ~2.9 times) and accumulation amount (4.7 ± 0.56% ID/g, ~2.3 times) in homotypic CT26 tumor compared to those (4.0 h in blood and 2.03 ± 0.60% ID/g in tumor) from uncoated Bi NPs. After 808 nm laser irradiation, CT26 cancer cells could be effectively ablated after the photothermal therapy of high-accumulated Bi@CCM NPs, and then the tumor tends to be eradicated after 12 days. Thus, Bi NPs camouflaged with CT26 CCM have great potential for the targeted photothermal therapy of homotypic tumors.

Single source precursor synthesized CuS nanoparticles for NIR phototherapy of cancer and photodegradation of organic carcinogen.

Herein, we report cost effective and body compatible CuS nanoparticles (NPs) derived from a single source precursor as photothermal agent for healing deep cancer and photocatalytic remediation of organic carcinogens. These NPs efficiently kill MCF7 cells (both in vivo and in vitro) under NIR irradiation by raising the temperature of tumor cells. Such materials can be used for the treatment of deep cancer as they can produce a heating effect using high wavelength and deeply penetrating NIR radiation. Furthermore, CuS NPs under solar light irradiation efficiently convert p-nitrophenol (PNP), an environmental carcinogen, to p-aminophenol (PAP) of pharmaceutical implication. In a nutshell, CuS can be used for the treatment of deep cancer and for the remediation of carcinogenic pollutants. There seems an intrinsic connection between the two functions of CuS NPs that need to be explored in length.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Chinese herbal medicine for vascular cognitive impairment in cerebral small vessel disease: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cerebral small vessel disease (CSVD) is the most common etiology of vascular cognitive impairment (VCI). VCI in CSVD (CSVD-VCI) shows a progressive course with multiple stages and is also associated with dysfunctions such as gait, emotional and behavioral, and urinary disturbances, which seriously affect the life quality of elderly people. In mainland China, Chinese herbal medicine (CHM) is clinically used for CSVD-VCI and presenting positive efficacy, but the evidence revealed in relevant clinical trials has not been systematically evaluated. The purpose of this study is to assess the current evidence available for the clinical efficacy and safety of CHM for CSVD-VCI. METHODS: A literature search of published RCTs up to April 30, 2020, has been conducted in the following 7 electronic databases: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technology Journals Database (VIP), Wanfang Database, and Chinese Biomedical Literature Service System (SinoMed). For unpublished studies, 2 clinical trial online registration websites will be searched: ClinicalTrials.gov and Chinese Clinical Trial Registry (ChiCTR). Only randomized controlled trials (RCTs) using CHM in the treatment of patients with CSVD-VCI, which compares CHM with no treatment, placebo, or other conventional treatments, will be included in this systematic review. Primary outcomes will be set as acknowledged scales measuring cognitive function. Secondary outcomes will involve activities of daily living, behavioral, and psychological symptoms, global performance of dementia, neurological function, biological markers of endothelial dysfunction, the clinical effective rate, and adverse events. After screening studies and extracting data, the Cochrane Collaborations tool for assessing risk of bias will be applied to assess the methodological quality of included RCTs. Review Manager Version 5.3 software will be used for data synthesis and statistical analysis. Subgroup analyses, sensitivity analyses, and meta-regression will be conducted to detect potential sources of heterogeneity. The funnel plot and Eggers test will be developed to evaluate publication bias, if available. We will perform the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to appraise the quality of evidence. RESULTS: Evidence exhibited in this systematic review will provide practical references in the field of CHM treating CSVD-VCI. Moreover, our detailed appraisals of methodological deficiencies of relevant RCTs will offer helpful advice for researchers who are designing trials of CHMs in the treatment of CSVD-VCI. CONCLUSION: The conclusion about the clinical efficacy and safety of CHM for CSVD-VCI will be provided for clinical plans, decisions, and policy developments in the full version of this systematic review. SYSTEMATIC REVIEW REGISTRATION: INPLASY202080120.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Correlation between Mitochondrial Dysfunction, Cardiovascular Diseases, and Traditional Chinese Medicine.

Cardiovascular disease (CVD) is the number one threat that seriously endangers human health. However, the mechanism of their occurrence is not completely clear. Increasing studies showed that mitochondrial dysfunction is closely related to CVD. Possible causes of mitochondrial dysfunction include oxidative stress, Ca2+ disorder, mitochondrial DNA mutations, and reduction of mitochondrial biosynthesis, all of which are closely related to the development of CVD. At present, traditional Chinese medicine (TCM) is widely used in the treatment of CVD. TCM has the therapeutic characteristics of multitargets and multipathways. Studies have shown that TCM can treat CVD by protecting mitochondrial function. Via systematic literature review, the results show that the specific mechanisms include antioxidant stress, regulation of calcium homeostasis, antiapoptosis, and regulation of mitochondrial biosynthesis. This article describes the relationship between mitochondrial dysfunction and CVD, summarizes the TCM commonly used for the treatment of CVD in recent years, and focuses on the regulatory effect of TCM on mitochondrial function.