Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

Effectiveness and safety of Qingfei Dayuan granules for treating influenza and upper respiratory tract infections manifested by the pulmonary heat-toxin syndrome: A multicenter, randomized, double-blind, placebo-controlled trial.

Background: Patients diagnosed with influenza and upper respiratory tract infections (URTIs) have similar clinical manifestations and biochemical indices and a low detection rate of viral pathogens, mixed infection with diverse respiratory viruses, and targeted antiviral treatment difficulty in the early stage. According to the treatment strategy of "homotherapy for heteropathy" in traditional Chinese medicine (TCM), different diseases with the same clinical symptoms can be treated with the same medicines. Qingfei Dayuan granules (QFDY), a type of Chinese herbal preparation included in the TCM Diagnosis and Treatment Protocol for COVID-19 of Hubei Province issued by the Health Commission of Hubei Province in 2021, are recommended for patients suffering from COVID-19 with symptoms of fever, cough, and fatigue, among others. Additionally, recent studies have shown that QFDY effectively alleviates fever, cough, and other clinical symptoms in patients with influenza and URTIs. Materials and methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial for treatment for influenza and URTIs manifested by pulmonary heat-toxin syndrome (PHTS) with QFDY. A total of 220 eligible patients were enrolled from eight first-class hospitals in five cities of Hubei Province in China and randomly assigned to receive either 15 g of QFDY or a placebo three times a day for 5 days. The primary outcome was the complete fever relief time. Secondary outcomes included efficacy evaluation of TCM syndromes, scores of TCM syndromes, cure rate of each single symptom, incidence of comorbidities and progression to severe conditions, combined medications, and laboratory tests. Safety evaluations mainly involved adverse events (AEs) and changes in vital signs during the study. Results: Compared with the placebo group, the complete fever relief time was shorter in the QFDY group, 24 h (12.0, 48.0) in the full analysis set (FAS) and 24 h (12.0, 49.5) in the per-protocol set (PPS) (p ≤ 0.001). After a 3-day treatment, the clinical recovery rate (22.3% in the FAS and 21.6% in the PPS) and cure rate of cough (38.6% in the FAS and 37.9% in the PPS), a stuffy and running nose, and sneezing (60.0% in the FAS and 59.5% in the PPS) in the QFDY group were higher than those in the placebo group (p < 0.05). The number of patients taking antibiotics for more than 24 h in the placebo group (nine cases) was significantly higher than that in the QFDY group (one case) (p < 0.05). There were no significant differences between the two groups in terms of scores of TCM syndromes, incidence of comorbidities or progression to severe conditions, combined use of acetaminophen tablets or phlegm-resolving medicines, and laboratory tests (p > 0.05). Meanwhile, no significant difference was found in the incidence of AEs and vital signs between the two groups (p > 0.05). Conclusion: The trial showed that QFDY was an effective and safe treatment modality for influenza and URTIs manifested by PHTS because it shortened the complete fever relief time, accelerated clinical recovery, and alleviated symptoms such as cough, a stuffy and running nose, and sneezing during the course of treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=131702, identifier ChiCTR2100049695.

A systematic review and meta-analysis of effect evaluation of traditional Chinese medicine in treating acute respiratory distress syndrome.

BACKGROUND: It was to systematically evaluate the effects of traditional Chinese medicine (TCM) in the treatment of acute respiratory distress syndrome (ARDS), and provide a theoretical basis for the clinical treatment of ARDS. METHODS: English databases of PubMed, Embase, Medline, Spring, Cochrane Library, and Web of Science were searched, and the randomized controlled trial literatures on the treatment of ARDS patients with TCM published from January 1, 2001 to December 31, 2020 were screened. Then, Cochrane Handbook 5.0.2 was employed to evaluate the risk of bias in the included literatures, and Review Manager 5.3 was utilized for meta-analysis. RESULTS: A total of 16 studies met the requirements and were included, with a total of 1,460 participants. The meta-analysis results showed that the mortality rate of patients in the observation group was remarkably reduced after treatment with TCM [mean deviation (MD) =0.51; 95% confidence interval (CI): 0.32-0.84; Z=2.69; P=0.007]. The effective rate of clinical treatment was improved (MD =2.64; 95% CI: 1.79-3.90; Z=4.90; P<0.00001). Arterial partial pressure of oxygen (PaO2) increased remarkably (MD =12.29; 95% CI: 8.88-15.71; Z=7.05; P<0.00001). The oxygenation index (PaO2/FiO2) increased remarkably (MD =50.70; 95% CI: 32.78-68.63; Z=5.54; P<0.00001). Interleukin-6 (IL-6) levels were remarkably reduced (MD =-8.32; 95% CI: -11.48 to -5.17; Z=5.17; P<0.00001). The level of C-reactive protein (CRP) decreased remarkably (MD =-9.23; 95% CI: -14.23 to -4.24; Z=3.62; P=0.0003). Compared with the control group, the above 8 analysis indicators showed statistically considerable differences. However, difference of partial pressure of carbon dioxide (PaCO2) level (MD =-0.16; 95% CI: -2.97-2.65; Z=0.11; P=0.91) was not obvious between groups. DISCUSSION: The treatment of ARDS with TCM can reduce the mortality rate of patients, improves the effective rate of clinical treatment, reduces the average mechanical ventilation time, increases the levels of PaO2, PaO2/FiO2, and reduces the levels of IL-6, tumor necrosis factor α (TNF-α), and CRP. The use of TCM has a significant treatment effect on ARDS.

Validated LC-MS/MS method for simultaneous quantification of seven components of Naodesheng in rat serum after oral administration and its application to a pharmacokinetic study.

A simple, precise and reliable LC-MS/MS method was developed and validated for simultaneous quantification of vitexin, notoginsenoside R1, hydroxysafflor yellow A, ginsenoside Rd, puerarin, daidzein and senkyunolide I as components of Naodesheng (NDS) in rat serum. The Linearity ranges in rat serum were 0.045-4.5 µg/mL for vitexin, 0.0476-4.76 µg/mL for notoginsenoside R1, 0.0422-4.22 µg/mL for hydroxysafflor yellow A, 0.0426-4.26 µg/mL for ginsenoside Rd, 0.0436-4.36 µg/mL for puerarin, 0.026-2.6 µg/mL for daidzein, and 0.05-5 µg/mL for senkyunolide I, with the correlation coefficients greater than 0.99. The established method was validated in terms of intra- and inter-day precision and accuracy, recovery, matrix effect and stability. Furthermore, the method was successfully applied for pharmacokinetic study of these seven components in rat serum after oral administration of NDS.

Determination of light-medium-heavy polycyclic aromatic hydrocarbons in vegetable oils by solid-phase extraction and high-performance liquid chromatography with diode array and fluorescence detection.

A new method for determination of 16 polycyclic aromatic hydrocarbons (PAHs)-naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3-cd]pyrene-in vegetable oils was developed. Solid-phase extraction (SPE) prior to high-performance liquid chromatography with fluorescence detection could be used for all those PAHs except acenaphthylene. Acenaphthylene could be detected using a diode array detector at 228 nm. The parameters and variables that affect the extraction were investigated. Under optimum conditions: the extract reagent was centrifuged at 4 °C and evaporated. After that a SPE procedure was used for further cleanup. The limits of detection and limits of quantification were in the range of 0.01-2.35 and 0.04-7.00 µg kg(-1) in vegetable oil, respectively. The relative standard deviations were under 5%.

[Clinical study on acupuncture for leukopenia induced by chemotherapy].

OBJECTIVE: To explore the adjunctive therapeutic effects of acupuncture for leukopenia induced by chemotherapy. METHODS Eighty six cases with leukopenia after chemotherapy treatment were randomly divided into a granulocyte colony-stimulating factor (G-CSF) plus acupuncture (A) group and a G-CSF group, 43 cases in each group. After chemotherapy treatments, the patients of both groups were treated with G-CSF for 4 times, with acupuncture at Zhigou (TE 6), Quchi (LI 11), Hegu (LI 4), etc. added in the G-CSF plus A group, for an observaion cycle of 45 days. Their therapeutic effects on the 10th and 31st day and peripheral white blood cell (WBC) counts and neutrophilic granulocyte classification on the 10th, 17th, 24th, 45th day after treatment were compared. RESULTS: After they were treated on the 10th day, the effective rates were both 100.0% (both 43/43), and on the 31st day, the effective rate of 98.9% (42/43) in the G-CSF plus A group was higher than 91.1% (35/43) in the G-CSF group (P < 0.05). The WBC counts in the G-CSF plus acupuncture group were both higher than those in the G-CSF group on the 10th, 17th and 24th day after treatment (all P < 0.05). The ratios of mature neutrophilic granulocyte in the G-CSF plus A group were all higher than those in the G-CSF group at the same time (all P < 0.01). CONCLUSION: Acupuncture can increase the therapeutic effect of G-CSF, delay the decrease of WBC after discontinuing G-CSF, promote the neutrophilic granulocyte differentiating forward to mature and it is better for improving leukopenia induced by chemotherapy.