Effect of YuPingFeng granules on clinical symptoms of stable COPD: study protocol for a multicenter, double-blind, and randomized controlled trial.

BACKGROUND: Reducing current clinical symptoms and the risks of future exacerbations is the main goal of stable COPD management. Traditional Chinese medicine has unique advantages in chronic disease management. YuPingFeng (YPF), as a classical prescription, has been proven to reduce the risk of exacerbations, but there is a lack of high-quality evidence for the assessment of clinical symptoms and quality of life, particularly for the assessment of treatment response of microecology and immunity. METHODS/DESIGN: This is a prospective, multicentre, randomized, double-blind, placebo-controlled clinical trial. A total of 316 eligible subjects with moderate to severe COPD will be randomized 1:1 to receive YPF or placebo. Participants will receive either YPF or a placebo at 5 g three times daily for 52 weeks. The primary outcome will be the change in the COPD Assessment Test (CAT) score after 52 weeks of treatment. Secondary outcomes will include changes in the St George's Respiratory Questionnaire (SGRQ) score and clinical symptom score, among others. Outcomes will be measured at each visit. The study will continue for 52 weeks and will include six visits to each subject (at day 0 and weeks 4,12,24,36 and 52). In the event of exacerbations, subjects will be required to go back to the hospital once on the first day of exacerbation or when their condition permits. DISCUSSION: This trial will provide research methods to evaluate the clinical efficacy, safety, and the possible mechanism of YPF in the treatment of stable moderate-to-severe COPD patients. In addition, we hope to provide more possibilities for TCM to participate in the management of stable COPD. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry on 3 June 2022 (ChiCTR2200060476; date recorded: 3/6/2022, https://www.chictr.org.cn/ ).

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Benzo(a)pyrene-induced mitochondrial respiration and glycolysis disturbance in human neuroblastoma cells.

Mammalian cells generate ATP through mitochondrial respiration and glycolysis. Mitochondria not only play a key role in cell energy metabolism but also in cell cycle regulation. As a neurotoxic pollutant, benzo(a)pyrene (BaP) can trigger neuronal oxidative damage and apoptosis. However, the features of BaP-induced energy metabolism disturbance in SH-SY5Y cells has rarely been addressed. This study aimed to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as indications of respiratory activities and glycolytic. SH-SY5Y cells were treated with BaP to establish a cytotoxicity model, and butylated hydroxy anisole (BHA) was used to alleviate the damages induced by BaP. Using the Seahorse Extracellular Flux analyzer (XFp), we found that BaP significantly reduced basal respiration, ATP-linked OCR in SH-SY5Y cells with dose- and time-dependent. BHA supplementation recovered the mitochondrial respiration, synchronously attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers, then rescued BaP-induced cell apoptosis. But long-term exposure to BaP or exposure to a high dosage of BaP could decrease OCR associated with maximal respiratory, spare capacity, and glycolysis metabolism. At the same time, the damage to cells is also more severe with the rate of apoptosis and mitochondrial membrane potential (ΔΨm) loss rising sharply, which were not entirely reversed by BHA. This study provides energy metabolism-related, indicative biomarkers of cytotoxicity induced by BaP, which might provide information for early prevention and intervention.

Cost-Effectiveness Analysis of the TCM "Yupingfeng Granules" in the Treatment of Acute Exacerbations of COPD Based on a Randomized Clinical Trial.

Introduction: Traditional Chinese medicine (TCM) is becoming increasingly important as it provides further options for treating many diseases worldwide. The TCM "Yupingfeng" has been used in China for over 800 years, and its clinical efficacy and safety for COPD treatment have been proven in previous studies. The objective of this study was to compare the long-term cost-effectiveness of Yupingfeng granules and the current conventional treatment for COPD patients in China. Methods: A Markov model was constructed from the perspective of the Chinese healthcare system using TreeAge Pro 2011. The model cycle length was 12 months, and the cycle time was set to 10 years. Data from a randomized controlled trial were used to generate the number of acute exacerbations, COPD assessment test (CAT) score and actual medication used. The state transition probabilities, costs and quality-adjusted life years (QALYs) were derived from available sources. A threshold of 72,447 yuan per QALY gained was used as a cost-effectiveness criterion. One-way and probabilistic sensitivity analyses were conducted to verify the model. In addition, the cost-effectiveness of a 35-year cycle was evaluated as a scenario analysis. Results: In the basic-case analysis, the ICER of adding Yupingfeng granules to the current conventional treatment drugs was ¥2123.04 per QALY, which was less than the threshold (one-time per capita GDP).Sensitivity analyses showed the results to be robust. Probabilistic sensitivity analysis showed that the probability of the ICER being less than the one-time per capita GDP threshold was 100%. In the scenario analysis, the incremental cost-effectiveness was ¥12,051.27 per QALY which was also under the one-time per capita GDP. Conclusion: By reducing the number of acute exacerbations of COPD, thereby correspondingly reducing the follow-up treatment cost, Yupingfeng granules combined with conventional treatment were found to provide a cost-effective therapeutic strategy for COPD.

A comprehensive analysis of the components of common weed pollen and related allergens in patients with allergic diseases in southern China.

BACKGROUND: Pollen allergens are vital contributors to allergic diseases. The frequency and coreactivity pattern of allergens are closely related to geographical distribution. OBJECTIVE: In this study, we aimed to characterize the prevalence of the molecular components of the common weed pollen allergens, birch pollen, walnut, and cross-reactive carbohydrate determinant (CCD), as well as investigate the relationship between the allergens and CCD in Chinese pollen-sensitized patients with allergic diseases. METHODS: Based on previous vegetation surveys, serum samples from 165 pollen-sensitized patients with allergic diseases in Guangdong Province in southern China were used to test 19 crude allergen extracts, their components, and CCD using component-resolved diagnosis (CRD). Moreover, the potential associations among CCD, allergens, and their components were described. RESULTS: In the 165 samples, the most common sensitized allergens were goosefoot (43.0%), ragweed (40.6%), walnut (37.6%), walnut tree (37.6%), and mugwort (37.0%), followed by platane (35.2%), cocklebur (27.9%), and birch (24.2%). The positivity rate of CCD was 39.4%. Among the samples positive for mugwort, 11 (18.0%), 15 (24.6%), and 15 (24.6%) were positive for Art v 1, Art v 2, and Art v 3, respectively. Among the 67 patients sensitized to ragweed, only five (7.5%) were positive for Amb a 1. In the 40 patients sensitized to birch, Bet v 2 had the highest positivity rate (40.0%). There were 62 patients who were sensitized to walnut. Their components had a lower positivity rate (less than 15%). The hierarchical clustering and optimal scale analysis showed that Art v 4 and Bet v 2 were closely related, and 91.9% of CCD-positive samples were polysensitized. Meanwhile, Spearman's rank correlation method showed that CCD was closely correlated with the sensitization of crude allergen extracts, and there was a low correlation between CCD and allergen components. CCD was highly correlated with goosefoot, ragweed, and walnut trees (r＞0.8). Moreover, there was a strong relationship between the levels of Jug r 3 and Art v 3 (r = 0.78; P < 0.001). CONCLUSIONS: In southern China, the weed pollens (ragweed, cocklebur, and goosefoot) exhibited higher positivity rates in adults and had a stronger relationship with CCD but not with mugwort. The positivity rate of allergen components was not high. CCD-positive samples were always polysensitized.

A ratiometric fluorescent nanoprobe for signal amplification monitoring of intracellular telomerase activity.

Telomerase is considered a valuable diagnostic and prognostic cancer biomarker. Accurate and reliable detection of telomerase activity is of great value in clinical diagnosis, screening of inhibitors, and therapeutics. Here, we developed a novel amplified fluorescence resonance energy transfer (FRET) nanoprobe for highly sensitive and reliable monitoring of intracellular telomerase activity. The nanoprobe (QDSA@DNA) was composed of a streptavidin-modified quantum dot (QDSA) which was functionalized with a telomerase primer sequence (TP) and Cy5-tagged signal switching sequence (SS) through biotin-streptavidin interaction. When the nanoprobe was assembled, the Cy5 was in close proximity to the QDSA, resulting in high FRET efficiency from the QDSA to Cy5. In the presence of telomerase, the TP could be extended to produce telomeric repeat units, which was complementary to the loop of SS. Thus, the SS could hybridize with elongated sequences to form a rigid double-stranded structure, which forced the Cy5 away from the surface of the QDSA, causing low FRET efficiency. Furthermore, due to the production of multiple repeat units by telomerase, multiple hairpin structures could be opened, yielding significant fluorescence ratio (FQDsa/FCy5) enhancement for sensing of telomerase activity. In this way, the combination of a FRET and target-assisted strategy in a nanoprobe improved the detection accuracy and amplified the detection signal, respectively. The QDSA@DNA nanoprobe also showed high selectivity, excellent nuclease stability, and good biocompatibility. More importantly, this nanoprobe was found to be an excellent platform for efficient monitoring of intracellular telomerase activity, providing a potential platform in tumor diagnosis and screening of telomerase-related inhibitors.

Respiratory nursing care with Angong Niuhuang pill for patients with chronic obstructive pulmonary disease following cardiac surgery.

AIM: Angong Niuhuang pill (ANP) is a traditional Chinese medicine (TCM) drug widely used for treating stroke. This study aimed to investigate the effect of ANP on respiratory nursing outcomes in chronic obstructive pulmonary disease (COPD) patients following cardiac surgery. METHODS: A total of 80 COPD patients following cardiac surgery were enrolled and randomized into the control group receiving routine postoperative nursing and ANP group additionally receiving ANP treatment for 3 days (n = 40 for both group). The frequency of back percussion, time of back percussion, amount of expectoration, arterial blood gas levels were compared between groups. RESULTS: Compared to the control group, the ANP group had a significantly shorter daily mean time of back percussion at day 3 (p = .036) and day 7 (p = .014). The daily mean amount of expectoration was higher at day3 (p = .018) but lower at day 7 (p = .043) in the ANP group than in the control group. In addition, the ANP group had significantly higher hemoglobin saturation (SpO2 ) and partial pressure of oxygen (PaO2 ) but lower partial pressure of carbon dioxide (PaCO2 ) at both day 3 and day 7 than the control group (all p < .05). Furthermore, the time of postoperative aerosol inhalations (p = .041), pulmonary infection rate (p = .025) and postoperative hospital stay (p = .036) were significantly reduced in the ANP group. The ANP group had significantly lower TCM symptom scores at day 3 and day 7 after surgery. CONCLUSION: These results suggested that ANP treatment can effectively promote the postoperative recovery and respiratory nursing outcomes in COPD patients following cardiac surgery.

Inhibitory Effect of Two Traditional Chinese Medicine Monomers, Berberine and Matrine, on the Quorum Sensing System of Antimicrobial-Resistant Escherichia coli.

The quorum sensing (QS) system controls bacterial biofilm formation, which is highly related to the virulence and resistance of pathogens. In the present study, the effect of two traditional Chinese medicine (TCM) monomers, berberine and matrine, on biofilm formation and QS-related gene expression of antimicrobial-resistant (AMR) Escherichia coli strains was investigated by laser scanning confocal microscopy (LSCM) observation and real-time PCR. The results indicated a roughly positive relationship between biofilm formation ability and antimicrobial resistance. LSCM observation showed that berberine and matrine inhibited biofilm formation of AMR E. coli strains at 1/2 minimal inhibitory concentration (MIC) (1/2 MIC berberine at OD630: 0.1020; 1/2 MIC matrine: OD630: 0.1045); furthermore, abnormal cell morphology such as rounded and elongated cells was also observed. This finding was consistent with the downregulation of QS-related genes: luxS, pfS, sdiA, hflX, motA, and fliA. At 1/2 MIC and 1/4 MIC concentrations of berberine, a significant downregulation of luxS, pfS, hflX, ftsQ, and ftsE was observed. The results indicate that berberine and matrine can inhibit biofilm formation by inhibiting the QS system and that berberine is more effective than matrine.

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study.

BACKGROUND: N-acetylcysteine (NAC) 600 mg twice daily is a well-tolerated oral antioxidant mucolytic that reduces the risk of moderate to severe chronic obstructive pulmonary disease (COPD) exacerbations. PANTHEON was one of the largest studies to evaluate NAC in COPD. It recruited current, ex- and never-smokers, concomitantly treated with other medications, and used a symptom-based definition of COPD exacerbations rather than the conventional healthcare resource utilisation (HCU) criteria. METHODS: This manuscript reports post-hoc analyses of the PANTHEON dataset investigating whether smoking status or use of concomitant medications influenced the efficacy of NAC in terms of reducing exacerbations, defined according to HCU. RESULTS: Compared with placebo (N = 482), NAC (N = 482) reduced the rate of HCU events by 20% (p = 0.0027), with a larger effect in current/ex-smokers (23%; p < 0.01). In patients receiving NAC and long-acting inhaled bronchodilator(s) but no ICS, there was a 60% reduction in the rate of exacerbations compared to those receiving placebo, long-acting bronchodilator(s) and ICS (p < 0.0001). CONCLUSIONS: Overall, these post-hoc hypothesis-generating analyses confirm that NAC reduces the rate of COPD exacerbations, particularly in patients with COPD who have a significant smoking history, and in those not treated with ICS. NAC may provide an alternative to ICS-containing combinations in these patient subgroups. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-TRC-09000460.

Effects of YuPingFeng granules on acute exacerbations of COPD: a randomized, placebo-controlled study.

PURPOSE: Recurrence of acute exacerbations has a major impact on patients with COPD. Therefore, effective prevention and treatment of exacerbation is crucial in the management of COPD, especially for patients with moderate to severe disease. This study evaluated the effectiveness of YuPingFeng granule administration in preventing exacerbation and improving symptom score, as well as its long-term (1 year) safety profile, in patients with COPD. PATIENTS AND METHODS: This was a randomized, double-blind, parallel, placebo-controlled study of 240 patients from eight centers in China. Participants were eligible if they had mild to severe COPD as defined by Global Initiative for Chronic Obstructive Lung Disease, had a history of at least two COPD exacerbations or one hospitalization within the previous year, and had remained clinically stable for over 4 weeks before the study. They were randomly assigned to receive 5 g of YuPingFeng or placebo, three times per day, for 1 year. The primary end point was the exacerbation rate over 1 year, and the analysis was by intention to treat. Secondary end points included symptom score, which was assessed by COPD assessment test (CAT) score and safety profiles. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; registration number: ChiCTR-IPR-15007023). RESULTS: The YuPingFeng group had a significantly lower exacerbation rate than the placebo group (1.15 vs 1.55; risk ratio=0.677 [95% CI 0.531-0.863]; P=0.002) and a significantly reduced risk of second exacerbation (95% CI 0.326-0.772; P=0.002). After treatment, the mean change in the CAT score in the YuPingFeng group (-4.41±7.01) differed significantly from that in the placebo group (-2.49±5.31; P=0.001). YuPingFeng was well tolerated. CONCLUSION: YuPingFeng granules can be considered as a treatment option for COPD; this treatment prevents acute exacerbations of COPD and has a good safety profile.

High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

Speciation analysis of selenium in rice samples by using capillary electrophoresis-inductively coupled plasma mass spectrometry.

An enzyme-assisted extraction used to extract all species of selenium in rice sample and a sensitive analytical method for the determination of ultratrace Se(VI), Se(IV), SeCys(2) (selenocystine) and SeMet (selenomethionine) with capillary electrophoresis-inductively coupled plasma mass spectrometry were firstly described in this study. The extraction method is simple, effective and can be used to extract trace selenium compounds in rice with high extraction efficiency and no altering its species. The analytical method has a detection limit of 0.1-0.9 ng Se/mL, and can be used to determine trace Se(VI), Se(IV), SeCys(2) and SeMet in rice directly without any derivatization and pre-concentration. With the help of above methods, we have successfully determined Se(VI), Se(IV), SeCys(2) and SeMet in selenium-enriched rice within 18 min with a recovery of 90-103% and a RSD (relative standard deviation, n=6) of 3-7%. Our results indicated that selenium-enriched rice contained only one species of selenium, SeMet, and its concentration is in range of 0.136-0.143 µg Se/g dried weight. The proposed method providing a realistic approach for the nutritional and toxical evaluation of different selenium compounds in nutritional supplements.