Efficacy and safety of Tanreqing injection for cough caused by acute trachea-bronchitis disease: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanreqing injection (TRQI) is an intravenous herbal preparation derived from 5 types of traditional Chinese medicines including Scutellariae Radix, Lonicerae Japonicae Flos, Forsythiae Fructus, bear bile powder and goral horn, incorporating baicalin, chlorogenic acid, ursodeoxycholic acid, and goose deoxycholic acid and other compounds known for anti-inflammatory properties, is widely used in China to treat cough caused by acute trachea-bronchitis disease (ATB). AIM OF THE STUDY: To investigate the clinical efficacy and safety of Tanreqing injection (TRQI) with and without Western medicine (WM) for cough caused by acute trachea-bronchitis (ATB). MATERIALS AND METHODS: We systematically searched eight databases, including CENTRAL, Embase, PubMed, Science Direct, Wiley, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and WanFang, from inception to August 2023 for randomized clinical trials (RCTs) on TRQI for cough caused by ATB. The critical outcomes of interest were time to symptom disappearance, including time for cough symptom to disappear and time to improve cough and sputum production. Important outcomes included symptom disappearance rate, adverse events (AEs) and lung function. We carried out random-effects meta-analysis using Review Manager 5.4 and assessed the certainty of evidence utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 2872 citations were identified by our search, of which 26 eligible RCTs enrolled 2731 participants. Low to moderate certainty evidence showed that when compared with WM, TRQI plus WM treatment was associated with a favorable effect on the time for cough symptom to disappear (MD -2.21 d, 95% CI -2.64 to -1.78), time to improve cough and sputum production (MD -0.68 d, 95% CI -0.83 to -0.53), symptom disappearance rate (RR 1.37, 95% CI 1.20 to 1.55), forced vital capacity, and forced expiratory volume in 1 s (MD 0.38 L, 95% CI 0.26 to 0.50; MD 2.92%, 95% CI 1.29 to 4.56, respectively). In terms of AEs, there was no association between TRQI plus WM and WM (RR 0.55, 95% CI 0.14 to 2.21; low-certainty evidence). Very low certainty evidence showed that TRQI alone was associated with reduced time to improve cough and sputum (MD -0.14 d, 95% CI -0.26 to -0.02) and increased symptom disappearance rate (RR 1.89, 95% CI 1.24 to 2.88; low certainty evidence) compared to WM. CONCLUSIONS: The overall efficacy of TRQI or WM for ATB cough is better than that of WM, and TRQI also effectively improve symptoms in patients with similar adverse events. However, due to the lack of methodological rigor of included studies, the present findings should be interpreted with caution. We advocate better high-quality and convincing clinical studies to be performed to prove the effectiveness and safety of TRQIs.

[Advances in pharmacological effects of jujuboside B].

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

[Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS].

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-ß-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-ß-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 µg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

Jian-Yan-Ling capsules ameliorate cognitive impairment in mice with D-galactose-induced senescence and inhibit the oxidation-induced apoptosis of HT22 hippocampal cells by regulating the Nrf2-HO1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jian-Yan-Ling (JYL) capsule is a famous anti-aging Chinese patent medicine. It is applied mainly to delay senescence to improve cognition in aging individuals. However, the action mechanisms of JYL for improving cognition have not been determined. AIM OF THE STUDY: We will evaluate the effect of the JYL capsule at improving the cognition of aging mice by improving oxidative stress in the hippocampus and exploring its action mechanism. MATERIALS AND METHODS: A senescence mouse model was developed via intraperitoneal injection of D-galactose. The effect of the JYL capsule at improving the learning and memory abilities of mice was evaluated using the Morris water maze and novel object recognition tests. The apotosis of model mice hippocampus' were determined by TUNEL analysis. The antioxidant capacity of the JYL capsule was evaluated by determining the activities of antioxidant enzymes and expressions of oxidative products. The regulation of the Nrf2/HO-1 signaling pathway of the JYL capsule was evaluated by determining the expressions of related proteins via western blotting analysis. In vitro, H2O2-treated mouse hippocampal HT22 cells were used to evaluate the antioxidant capacity of JYL-containing rat serum by determining the cell viability, apoptotic level and expressions of related proteins. RESULTS: JYL capsules enhanced the learning and memory abilities of model mice according to behavioral tests. The results of TUNEL analysis showed that the JYL capsule ameliorated hippocampal apoptosis in model mice. JYL capsules also exerted significant antioxidant capacity by increasing the activities of antioxidant enzymes while decreasing the levels of oxidative products both in the hippocampus and serum. The regulation of Nrf2/HO-1 pathway might contribute to the antioxidant function. In vitro, JYL-containing rat serum protected HT22 cells from H2O2 induced oxidative stress. The apoptosis of HT22 cells was also attenuated by regulating the caspase and Nrf2/HO-1 signaling pathways. CONCLUSIONS: The amelioration of neuronal oxidative stress of hippocampus might contribute to the D-galactose-induced cognition impairment of senescence mice. These findings provide evidence for the application of JYL capsules to enhance cognition in aging individuals.

Advances for pharmacological activities of Polygonum cuspidatum - A review.

CONTEXT: Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name 'Huzhang', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc. OBJECTIVE: This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts. METHODS: The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords. RESULTS: The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns. CONCLUSIONS: Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.

Protective effects of Lycium barbarum L. berry extracts against oxidative stress-induced damage of the retina of aging mouse and ARPE-19 cells.

In this study, we investigated the preventive effect of Lycium barbarum L. berry extract on age-related macular degeneration (AMD) and the main components responsible for its antioxidant activity. An AMD mouse model was developed by feeding 18-month-old mice with a 1% hydroquinone diet. Meanwhile, the model mice were treated with water extract (LBW) and alcohol extract (LBE) of L. barbarum berries respectively for 3 months. It was found that the retinal structural abnormalities were improved and the oxidation stress and inflammatory imbalance were both attenuated in model mice treated with the extracts of L. barbarum berries. According to the metabolomics analysis of the serum of model mice, LBW regulated the metabolism of unsaturated fatty acids and sphingolipids, while LBE extracts tended to regulate taurine metabolism. On sodium iodate induced oxidative injury of ARPE-19 cells, water extracts of L. barbarum berries eluted with 95% ethanol (LBW-95E) on AB-8 macroporous resin significantly improved the cell viability and attenuated oxidative stress by increasing the superoxide dismutase (SOD) activity and glutathione (GSH) content, decreasing the reactive oxygen species (ROS) content, promoting the entry of nuclear factor erythroid-derived 2-like 2 (Nrf2) into the nucleus and up-regulating the heme oxygenase-1 (HO-1) expression. Scopoletin, N-trans-feruloyltyramine and perlolyrine were identified as the main components of LBW-95E. These results demonstrated that L. barbarum berry extracts protected the retina of aging AMD model mice from degeneration and LBW-95E was the vital antioxidant activity fraction of LBW. These findings suggest that L. barbarum berry extracts might be an excellent natural source for the development of retinal protection-related drugs or dietary supplements.

Safety assessment of oil extracted from lacquer (Toxicodendron vernicifluum (Stokes) F.A. Barkley) seed: acute and subchronic toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicodendron vernicifluum (Stokes) F.A. Barkley (RVS) is an economic tree species and widely distributed in East Asia. Wood parts and raw lacquers of RVS have been used in coatings, herbal medicines or food supplements, and the leaves, flowers, roots, and fruits of RVS are also widely used in medicine traditionally. Lacquer seed oil (LSO) has potential health benefits and has not previously been evaluated for safety. AIM OF THE STUDY: The aim of the present study was to investigate the toxicological potential of LSO by acute and subchronic toxicity tests. MATERIALS AND METHODS: The characterization of fatty acids of the LSO was carried out by gas chromatography. In the acute toxicity study, LSO was administered at single doses of 5000 or 10000 mg/kg by oral gavage. The subchronic toxicity study was conducted by daily oral administration of LSO at doses of 1250, 2500 and 5000 mg/kg/day for 30 consecutive days. The animals were evaluated for clinical observations, body weight, organ weight, feed consumption, biochemical and hematological parameters, and liver, lung, and kidney histology. RESULTS: There were no mortality and toxic changes were observed in acute toxicity study. The results of subchronic toxicity showed no toxicologically significant changes in clinical observations, body weight, organ weight, biochemical or hematological parameters. Histopathologic results indicated slight hepatic steatosis and inflammatory infiltration in the rats of 5000 mg/kg/day LSO treated group. However, the histopathologic observation was not confirmed by hepatic biochemical analysis. CONCLUSIONS: These results suggested that the LD50 of LSO is over 10000 mg/kg and LSO is non-toxic for SD rats in acute toxicity study. The no observed adverse effect level (NOAEL) of LSO in rats is considered to be 5000 mg/kg/day, and liver is the potential target organ of LSO for 30-day subchronic toxicity study.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20-50 nm) and M40 (20-50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Comparative efficacy and safety of antiviral traditional Chinese medicine injections for viral pneumonia: a systematic review and network meta-analysis.

BACKGROUND: Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP. RESEARCH DESIGN AND METHODS: Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes. RESULTS: A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP. CONCLUSIONS: This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.

The synergistic compatibility mechanisms of fuzi against chronic heart failure in animals: A systematic review and meta-analysis.

Background: Fuzi's compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms. Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions. Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dtmax, -dP/dtmax, TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration. Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo, and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model-effect and time-effect relationships.

Efficacy and safety of chinese herbal medicine for treating mild or moderate COVID-19: A systematic review and meta-analysis of randomized controlled trials and observational studies.

Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients. Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%); shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs); increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant. Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.

The Chinese herb Styrax triggers pharmacokinetic herb-drug interactions via inhibiting intestinal CYP3A.

Human cytochrome P450 3A4 (hCYP3A4) is a predominant enzyme to trigger clinically relevant drug/herb-drug interactions (DDIs or HDIs). Although a number of herbal medicines have been found with strong anti-hCYP3A4 effects in vitro, the in vivo modulatory effects of herbal medicines on hCYP3A4 and their potential risks to trigger HDIs are rarely investigated. Herein, we demonstrate a case study to efficiently find the herbal medicine(s) with potent hCYP3A4 inhibition in vitro and to accurately assess the potential HDIs risk in vivo. Following screening over 100 herbal medicines, the Chinese herb Styrax was found with the most potent hCYP3A4 inhibition in HLMs. In vitro assays demonstrated that Styrax could potently inhibit mammalian CYP3A in liver and intestinal microsomes from both humans and rats. In vivo pharmacokinetic assays showed that Styrax (i.g., 100 mg/kg) significantly elevated the plasma exposure of two CYP3A-substrate drugs (midazolam and felodipine) when midazolam or felodipine was administered orally. By contrast, the plasma exposure of either midazolam or felodipine was hardly affected by Styrax (i.g.) when the victim drug was administered intravenously. Further investigations demonstrated that seven pentacyclic triterpenoid acids (PTAs) in Styrax were key substances responsible for CYP3A inhibition, while these PTAs could be exposed to intestinal tract at relatively high exposure levels but their exposure levels in rat plasma and liver were extremely low. These findings well explained why Styrax (i.g.) could elevate the plasma exposure of victim drugs only when these agents were orally administrated. Collectively, our findings demonstrate that Styrax can modulate the pharmacokinetic behavior of CYP3A-substrate drugs via inhibiting intestinal CYP3A, which is very helpful for the clinical pharmacologists to better assess the HDIs triggered by Styrax or Styrax-related herbal products.

Role of Traditional Chinese Medicine in Treating Severe or Critical COVID-19: A Systematic Review of Randomized Controlled Trials and Observational Studies.

Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China; a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias. Results: The search yielded 217,761 records, and 21 studies (6 RCTs and 15 observational studies) proved eligible. A total of 21 studies enrolled 12,981 severe/critical COVID-19 patients with a mean age of 57.21 years and a mean proportion of men of 47.91%. Compared with usual supportive treatments, the effect estimates of TCM treatments were consistent in direction, illustrating that TCM treatments could reduce the risk of mortality, rate of conversion to critical cases, and mechanical ventilation, and showed significant advantages in shortening the length of hospital stay, time to viral clearance, and symptom resolution. The results were similar when we restricted analyses to low-risk-bias studies. No serious adverse events were reported with TCM treatments, and no significant differences were observed between groups. Conclusion: Encouraging evidence suggests that TCM presents substantial advantages in treating severe/critical COVID-19 patients. TCM has a safety profile that is comparable to that of conventional treatment alone. TCMs have played an important role in China's prevention and treatment of COVID-19, which sets an example of using traditional medicine in preventing and treating COVID-19 worldwide.

Role of Licochalcone A in Potential Pharmacological Therapy: A Review.

Licochalcone A (LA), a useful and valuable flavonoid, is isolated from Glycyrrhiza uralensis Fisch. ex DC. and widely used clinically in traditional Chinese medicine. We systematically updated the latest information on the pharmacology of LA over the past decade from several authoritative internet databases, including Web of Science, Elsevier, Europe PMC, Wiley Online Library, and PubMed. A combination of keywords containing "Licochalcone A," "Flavonoid," and "Pharmacological Therapy" was used to help ensure a comprehensive review. Collected information demonstrates a wide range of pharmacological properties for LA, including anticancer, anti-inflammatory, antioxidant, antibacterial, anti-parasitic, bone protection, blood glucose and lipid regulation, neuroprotection, and skin protection. LA activity is mediated through several signaling pathways, such as PI3K/Akt/mTOR, P53, NF-κB, and P38. Caspase-3 apoptosis, MAPK inflammatory, and Nrf2 oxidative stress signaling pathways are also involved with multiple therapeutic targets, such as TNF-α, VEGF, Fas, FasL, PI3K, AKT, and caspases. Recent studies mainly focus on the anticancer properties of LA, which suggests that the pharmacology of other aspects of LA will need additional study. At the end of this review, current challenges and future research directions on LA are discussed. This review is divided into three parts based on the pharmacological effects of LA for the convenience of readers. We anticipate that this review will inspire further research.

Granular indigenous microalgal-bacterial consortium for wastewater treatment: Establishment strategy, functional microorganism, nutrient removal, and influencing factor.

Granular indigenous microalgal-bacterial consortium (G-IMBC) system integrates the advantages of the MBC and granular activated sludge technologies, also with superior microalgal wastewater adaptation capacity. In this review, the concept of IMBC was firstly described, followed by its establishment and acclimation strategies. Characteristics and advantages of G-IMBC system compared to other IMBC systems (i.e., attached and floc IMBC systems) were then introduced. Moreover, the involved functional microorganisms and their interactions, as well as nutrient removal mechanisms were systematically and critically reviewed. Finally, the influencing factors including wastewater characteristics and operation factors were discussed. This study aims to provide a comprehensive up-to-date summary of the G-IMBC system for sustainable wastewater treatment.

Blockade of GCH1/BH4 Axis Activates Ferritinophagy to Mitigate the Resistance of Colorectal Cancer to Erastin-Induced Ferroptosis.

Ferroptosis, a type of cell death triggered by excessive accumulation of iron-dependent lipid peroxidation, possesses an excellent potential in cancer treatment. However, many colorectal cancer (CRC) cell lines are resistant to ferroptosis induced by erastin and RSL3, the classical ferroptotic inducers. Moreover, the underlying mechanism of resistance remains poorly elucidated. This study sought to discover the major factor contributing to ferroptosis resistance in CRC. The study findings will help design strategies for triggering ferroptosis for application in individualized tumor therapy. Here, we show that tetrahydrobiopterin (BH4) determines the sensitivity of CRC cells to ferroptosis induced by erastin. GTP cyclohydrolase-1 (GCH1) is the first rate-limiting enzyme of BH4. Genetic or pharmacological inhibition of GCH1 decreased BH4 and assisted erastin in cell death induction, lipid peroxidation enhancement, and ferrous iron accumulation. BH4 supplementation completely inhibited ferroptotic features resulting from GCH1 knockdown. Unexpectedly, GCH1 knockdown failed to enhance RSL3-induced cell death in CRC. Mechanistically, GCH1 knockdown drastically activated ferritinophagy during erastin treatment rather than RSL3 treatment. Administration of an autophagy inhibitor reversed erastin resistance in GCH1-knockdown cells. GCH1 inhibitor and erastin co-treatment in vivo synergistically inhibited tumor growth in CRC. Overall, our results identified GCH1/BH4 metabolism as a burgeoning ferroptosis defense mechanism in CRC. Inhibiting GCH1/BH4 metabolism promoted erastin-induced ferroptosis by activating ferritinophagy, suggesting that combining GCH1 inhibitors with erastin in the treatment of CRC is a novel therapeutic strategy.

[Proposal of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19].

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation.

PURPOSE: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. METHODS: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5'-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. RESULTS: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. CONCLUSION: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.

Efficacy and Safety of Qingfei Paidu Decoction for Treating COVID-19: A Systematic Review and Meta-Analysis.

Background: Qingfei Paidu decoction (QFPD) has been widely used in treating COVID-19 in China. However, there is still a lack of comprehensive and systematic evidence to demonstrate the effectiveness and safety of QFPD. This study aims to evaluate the efficacy and safety of QFPD in patients with COVID-19. Methods: We searched seven databases up to 5 March 2021. Two reviewers independently screened studies, extracted data of interest, and assessed risk of bias. The Cochrane risk of bias tool was used to assess the risk of bias of randomized controlled trials. The Newcastle-Ottawa scale was used to assess the risk of bias of cohort and non-randomized trials. The "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" was adopted for controlled pre-post studies. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of evidence. We carried out a random effect meta-analysis using RevMan 5.3. For outcomes that could not be meta-analyzed, we performed a descriptive analysis. Results: We identified 16 studies with 11,237 patients, including one RCT, six non-randomized trials, two cohort studies, and seven pre-post studies. The certainty of evidence was low to very low because of the observational study design. QFPD combined with conventional treatment might decrease the time for nucleic acid conversion (MD = -4.78 days, 95% CI: -5.79 to -3.77), shorten the length of hospital stay (MD = -7.95 days, 95% CI: -14.66 to -1.24), shorten the duration of symptoms recovery of fever (MD = -1.51 days, 95% CI: -1.92 to -1.09), cough (MD = -1.64 days, 95% CI: -1.91 to -1.36) and chest CT (MD = -2.23 days, 95% CI: -2.46 to -2.00), improve the overall traditional Chinese medicine symptom scores (MD = 41.58 scores, 95% CI: 32.67 to 50.49), and change the laboratory indexes, such as WBC, AST, and CRP. Conclusion: QFPD combined with conventional treatment might be effective for patients with COVID-19. No serious adverse reactions related to QFPD were observed. Further high-quality studies are still needed in the future.