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ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Baidu Powder (JFBDP) is a classic traditional Chinese medicine prescription. Although Jingfang Baidu powder obtained a general consensus on clinical efficacy in treating pneumonia, there were many Chinese herbal drugs in formula, complex components, and large oral dosage, which brings certain obstacles to clinical application. AIM OF THE STUDY: Therefore, screening of the active fraction that exerts anti-pneumonia helps improve the pharmaceutical preparation, improve the treatment compliance of patients, and further contribute to the clinical application, and the screening of the new active ingredients with anti-pneumonia. The histopathological observation, real-time quantitative PCR, western blotting, and immunofluorescence were applied to evaluate the anti-pneumonia efficacy of active fractions from JFBDP. RESULTS: Three fractions from JFBDP inhibit the gene expression of IL-1ß, IL-10, CCL3, CCL5, and CCL22 in lung tissue infected by Klebsiella at various degrees, and presented a good dose-response relationship. JF50 showed stronger anti-inflammatory effects among three fractions including JF30, JF50, and JF75. Besides, JF50 significantly reduced the protein expression of TLR4 and Myd88 in lung tissue infected with Klebsiella, and it also significantly inhibited p-ERK and p-NF-κB p65. JF50 significantly inhibits the protein expression of Caspase 3, Caspase 8, and Caspase 9 in lung tissue infected with Klebsiella at the dose of 25 mg/kg and 50 mg/kg. CONCLUSION: JF50 improves lung pathological damage in Klebsiella pneumonia mice by inhibiting the TLR4/Myd88/NF-κB-ERK signaling pathway, and inhibiting apoptosis of lung tissue cells. These findings provide a reference for further exploring the active substance basis of Jingfang Baidu Powder in treating bacterial pneumonia.
Subject(s)
Drugs, Chinese Herbal , Klebsiella Infections , Myeloid Differentiation Factor 88 , Powders , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Myeloid Differentiation Factor 88/metabolism , Mice , Male , Klebsiella Infections/drug therapy , MAP Kinase Signaling System/drug effects , Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , Lung/drug effects , Lung/pathology , Lung/metabolism , Klebsiella pneumoniae/drug effects , Signal Transduction/drug effects , Mice, Inbred C57BLABSTRACT
This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.
Subject(s)
Drugs, Chinese Herbal , Pneumonia , Aged , Humans , Cough/chemically induced , Drugs, Chinese Herbal/adverse effects , Pneumonia/drug therapy , Reproducibility of Results , Randomized Controlled Trials as TopicABSTRACT
Objectives: Pathogenic organisms utilize iron to survive and replicate and have evolved many processes to extract iron from human hosts. The goal of this study was to elucidate the impact of iron supplementation given in the setting of acute infection. Methods: This was a retrospective cohort study of Veterans Affairs patients who received intravenous antibiotics for pneumonia or skin and skin structure infections. Five-thousand subjects were included in each of the 2 cohorts: iron-receiving and non-iron-receiving. Data was analyzed using Fischer's Exact test if categorical and independent t-tests if continuous. Primary and secondary objectives analyzed with Cox proportional hazard regression and outcome rates estimated utilizing Kaplan-Meier method. Results: Five-thousand patients were included in each cohort. The iron cohort was significantly older (Mean-years: Iron = 71.6, No-iron = 68.9; mean-difference = 2.7, P < .0001) with reduced renal function (Mean-eGFR[mL/min/1.73 m²]: Iron = 67.2, No-iron = 77.4; mean-difference = 10.2, P < .0001). For the primary outcome, the iron cohort had a significantly longer mean length of hospital stay (10.4 days) compared to the no-iron cohort (8.7 days) (mean difference 1.7 days, P < .0001). Secondary outcome analysis showed the iron cohort received intravenous antibiotics for longer (Iron = 8.2 days, No-iron = 7.1 days; mean-difference = 1.1 days, P < .0001) with a higher proportion of 30-day readmissions (Iron = 15.6%, No-iron = 12.8%; proportion difference = 2.8%, P < .0001). No significant difference was found between cohort proportions for 30-day mortality (Iron = 12.7%, No-iron = 11.3%, proportion difference = 1.4%, P = .052). Conclusions: Baseline characteristic differences between cohorts is representative of patients who would be expected to require iron replacement therapy. Given the magnitude of primary and secondary-outcomes, further studies controlling for these factors would be warranted.
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Pneumonia is a major public health problem for older adults, being one of the leading causes of hospitalization and death, particularly for elderly nursing home residents. We previously conducted a clinical trial in which we demonstrated that 29% of nursing home residents had low serum zinc levels coinciding with a two-fold increase in pneumonia incidence and duration in comparison to individuals with adequate serum zinc levels. However, causality could not be inferred and necessitates a double-blind clinical trial. To determine the appropriate supplementation dose for such a trial we are conducting a randomized, placebo-controlled, double-blind clinical pilot trial aimed at delineating the optimal dosage (30 and 60 mg/day elemental Zn) and establishing safety. The results from the pilot study will be leveraged to inform our larger randomized clinical trial designed to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on respiratory infections, antibiotic use, and duration of sick days with pneumonia. In tandem with dose optimization, we will evaluate the correlation between serum zinc and pan-T cell zinc levels, given that T cells and their zinc levels are important in the response and resolution of respiratory infections but whose correlation has only been extrapolated and not demonstrated. Herein we present the study rationale and protocol, as well as discuss specific challenges we encountered in securing a manufacturer for the study agents and when recruiting from nursing home populations during the COVID-19 pandemic. In light of these experiences, we provide recommendations for future clinical trials under circumstances where supply chains are disrupted, and recruitment pools are constrained or unavailable. Clinical trial registration: https://clinicaltrials.gov/, NCT05527899.
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The epidemic prompted by COVID-19 continues to spread, causing a great risk to the general population's safety and health. There are still no drugs capable of curing it. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the two other diseases caused by coronaviruses. Traditional Chinese Medicine (TCM) showed benefits in treating SARS and MERS by preventing the disease early, substantially mitigating symptoms, shortening the treatment period, and minimizing risks and adverse reactions caused by hormone therapy. Although several vaccines have been developed and are being used for the treatment of COVID-19, existing vaccines cannot provide complete protection against the virus due to the rapid evolution and mutation of the virus, as mutated viral epitopes evade the vaccine's target and decrease the efficacy of vaccines. Thus, there is a need to develop alternative options. TCM has demonstrated positive effects in the treatment of COVID-19. Previous research studies on TCM showed broad-spectrum antiviral activity, offering a range of possibilities for their potential use against COVID-19. This study shed some light on common TCM used for SARS and MERS outbreaks and their effective use for COVID-19 management. This study provides new insights into COVID-19 drug discovery.
Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Drugs, Chinese Herbal , Medicine, Chinese Traditional , SARS-CoV-2 , Humans , Medicine, Chinese Traditional/methods , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Pharmacopoeias as TopicABSTRACT
BACKGROUND: Vitamin D supplementation for infectious diseases has been discussed, but its role in COVID-19 is unclear. Therefore, this study examined the clinical outcomes of COVID-19 pneumonia patients who received vitamin D supplementation. METHODS: This prospective, open-label, randomized controlled trial was conducted in a university hospital between July 2020 and March 2022. The inclusion criteria were patients aged ≥ 18 years with COVID-19 pneumonia patients. The patients were randomized into two groups: an intervention group receiving vitamin D supplementation (alfacalcidol, two mcg orally daily) until discharge and a control group. The clinical outcomes were pneumonia treatment duration, length of hospital stay, and change in pneumonia severity index between enrollment and discharge. Subgroup analysis was conducted for supplemental oxygen use, high-dose corticosteroid administration, evidence of lymphopenia, C-reactive protein concentration, and total serum vitamin D concentration. Adverse events were monitored. RESULTS: Two hundred ninety-four patients were recruited (147 per group). The two groups did not differ in pneumonia treatment duration to discharge (p = 0.788) or length of hospital stay (p = 0.614). The reduction in the pneumonia severity index between enrollment and discharge was more significant in the intervention group (p = 0.007); a significant decrease was also observed among patients who had C-reactive protein > 30 mg/L (p < 0.001). No adverse reactions were recorded. CONCLUSIONS: Adding active vitamin D to standard treatment may benefit COVID-19 pneumonia patients who require supplemental oxygen or high-dose corticosteroid therapy or who have high C-reactive protein concentrations (> 30 mg/L) upon treatment initiation. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210906005 (retrospectively registered, 6 September 2021).
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Prospective Studies , C-Reactive Protein , Vitamin D/therapeutic use , Dietary Supplements , Adrenal Cortex Hormones/therapeutic use , OxygenABSTRACT
BACKGROUND: The emergence of carbapenem-resistant and extensively drug-resistant (XDR) Acinetobacter baumannii as well as inadequate effective antibiotics calls for an urgent effort to find new antibacterial agents. The therapeutic efficacy of two human scFvs, EB211 and EB279, showing growth inhibitory activity against A. baumannii in vitro, was investigated in immunocompromised mice with A. baumannii pneumonia. RESULTS: The data revealed that infected mice treated with EB211, EB279, and a combination of the two scFvs showed better survival, reduced bacterial load in the lungs, and no marked pathological abnormalities in the kidneys, liver, and lungs when compared to the control groups receiving normal saline or an irrelevant scFv. CONCLUSIONS: The results from this study suggest that the scFvs with direct growth inhibitory activity could offer promising results in the treatment of pneumonia caused by XDR A. baumannii.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Pneumonia , Single-Chain Antibodies , Humans , Animals , Mice , Single-Chain Antibodies/pharmacology , Single-Chain Antibodies/therapeutic use , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pneumonia/drug therapy , Pneumonia/microbiology , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity TestsABSTRACT
Background: A patient with severe COVID-19 pneumonia had adjunctive acupuncture to improve respiration and facilitate weaning off prolonged mechanical ventilation (MV). Case: A man in his 40s with COVID-19 was in an advanced critical-care center on symptom day 5 for respiratory failure due to pneumonia requiring MV therapy. He received high-dose corticosteroid pulse therapy, antiviral agents, and multiple antibiotics for complicated bacterial pneumonia and bacteremia. Repeated MV weaning attempts failed, although his pneumonia gradually improved. Then, acupuncture 4 times per week was started to improve his respiration and facilitate MV weaning from day 49 of his symptoms' onset. Results: His weaning-related indices improved, including reductions in respiratory rate and Rapid Shallow Breath Index. His O2 saturation increased immediately after each acupuncture treatment. The day after the first acupuncture treatment, his MV support was reduced by changing ventilation mode from synchronized intermittent mandatory ventilation mode to continuous positive airway pressure (CPAP) mode during the day without exacerbation of respiratory status. After 3 days of acupuncture, this patient was on CPAP support alone. MV therapy was discontinued completely after 8 days of acupuncture (6th acupuncture treatment). Conclusions: Acupuncture improved respiration and facilitated MV weaning in a patient with respiratory failure secondary to COVID-19. Adjunctive acupuncture may benefit such patients and others after severe pneumonia. Large cohort studies are needed.
ABSTRACT
BACKGROUND: Community-acquired pneumonia (CAP) poses a significant global health challenge, even more so for children less than five years old. Nutritional interventions, such as zinc and vitamin A supplementation, are gaining attention for their therapeutic potential in enhancing recovery and minimizing pneumonia severity in pediatric patients. OBJECTIVE: To assess the therapeutic benefits of zinc and vitamin A supplementation in pediatric CAP patients under five years old and to advocate for their use in clinical settings. METHODOLOGY: Three groups were formed in a randomized controlled trial conducted from October 2022 to September 2023, to address zinc and vitamin A supplementation in pediatric patients under five years old in the intensive care unit with severe pneumonia. Group 1 received zinc supplementation, group 2 received vitamin A supplementation, and group 3 served as the control group, receiving antibiotic treatment exclusively for pneumonia. This treatment comprised either a ß-lactam (amoxicillin-clavulanate, commonly referred to as Augmentin) administered orally at 500 mg/125 mg three times a day, Augmentin 875 mg/125 mg orally twice daily, or Augmentin 2000 mg/125 mg orally once daily. Additionally, the control group received a macrolide (azithromycin or clarithromycin) or doxycycline at a dosage of 100 mg orally twice daily. Linear regression analysis identified statistically significant decreases in both length of hospital stay and active pneumonic effusion. RESULTS: The study encompassed 90 pediatric pneumonia patients with an age range of six to 55 months. Multiple linear regression analysis showed that both vitamin A and zinc led to a significant decrease in hospitalization length by 2.39 days (p < 0.01, 95% CI: 4.19-0.47) and 3.17 days (p < 0.01, 95% CI: 5.19-1.31), respectively. In comparison to the control group, both the vitamin A and zinc supplementation groups were linked to a shorter pneumonic effusion duration (p < 0.001). CONCLUSION: Both interventions significantly reduced the duration of hospitalization (2.39 days for vitamin A and 3.17 days for zinc) and pneumonic effusion compared to the control group. These findings highlight the potential of zinc and vitamin A as valuable additions to standard CAP treatment regimens, potentially leading to improved clinical outcomes and reduced healthcare burdens.
ABSTRACT
This study examined the association between the number of nursing staff in intensive care units (ICUs) and hospital-acquired pneumonia (HAP) among surgical patients in South Korea. Data were obtained between 2008 and 2019 from the Korean National Health Insurance Service Cohort Database; 37,706 surgical patients who received critical care services were included in the analysis. Patients with a history of pneumonia 1 year prior to surgery or those who had undergone lung-related surgery were excluded. The ICU nursing management fee is an admission fee that varies based on the grading determined by nurse-to-bed ratio. Using this grading system, we classified four groups from the highest to the lowest level based on the proportion of beds to nurses (high, high-mid, mid-low, and low group). HAP was defined by the International Classification of Disease, 10th revision (ICD-10) code. Multilevel logistic regression was used to investigate the relationship between the level of ICU nurse staffing and pneumonia, controlling for variables at the individual and hospital levels. Lower levels of nurse staffing were associated with a greater incidence of HAP than higher levels of nurse staffing (mid-high, OR: 1.33, 95% CI: 1.12-1.57; mid-low, OR: 1.61, 95% CI: 1.27-2.04; low, OR: 2.13, 95% CI: 1.67-2.71). The intraclass correlation coefficient value was 0.177, and 17.7% of the variability in HAP was accounted for by the hospital. Higher ICU nursing management fee grades (grade 5 and above) in general and hospital settings were significantly associated with an increased risk of HAP compared to grade 1 admissions. Similarly, in tertiary hospitals, grade 2 and higher ICU nursing management fees were significantly associated with an increased risk of HAP compared to grade 1 admissions. Especially, a lower level of nurse staffing was associated with bacterial pneumonia but not pneumonia due to aspiration. In conclusion, this study found an association between the level of ICU nurse staffing and HAP among surgical patients. A lower level of nurse staffing in the ICU was associated with increased rates of HAP among surgical patients. This indicates that having fewer beds assigned to nurses in the ICU setting is a significant factor in preventing HAP, regardless of the size of the hospital.
Subject(s)
Nursing Staff, Hospital , Pneumonia , Humans , Republic of Korea , Intensive Care Units , Tertiary Care Centers , Critical Care , National Health Programs , WorkforceABSTRACT
Klebsiella pneumoniae is a type of Gram-negative bacteria that causes a variety of infections, including pneumonia, bloodstream infections, wound infections, and meningitis. The treatment of K. pneumoniae infection depends on the type of infection and the severity of the symptoms. Antibiotics are generally used to treat K. pneumoniae infections. However, some strains of K. pneumoniae have become resistant to antibiotics. This comprehensive review examines the potential of natural compounds as effective strategies against K. pneumonia infections. The alarming rise in antibiotic resistance underscores the urgent need for alternative therapies. This article represents current research on the effects of diverse natural compounds, highlighting their anti-microbial and antibiofilm properties against K. pneumonia. Notably, compounds such as andrographolide, artemisinin, baicalin, berberine, curcumin, epigallocatechin gallate, eugenol, mangiferin, piperine, quercetin, resveratrol, and thymol have been extensively investigated. These compounds exhibit multifaceted mechanisms, including disruption of bacterial biofilms, interference with virulence factors, and augmentation of antibiotic effectiveness. Mechanistic insights into their actions include membrane perturbation, oxidative stress induction, and altered gene expression. While promising, challenges such as limited bioavailability and varied efficacy across bacterial strains are addressed. This review further discusses the potential of natural compounds as better alternatives in combating K. pneumonia infection and emphasizes the need for continued research to harness their full therapeutic potential. As antibiotic resistance persists, these natural compounds offer a promising avenue in the fight against K. pneumonia and other multidrug-resistant pathogens.
Subject(s)
Klebsiella Infections , Pneumonia , Humans , Klebsiella pneumoniae , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Molecular Structure , Anti-Bacterial Agents/pharmacology , Pneumonia/drug therapy , Pneumonia/microbiology , Drug Resistance , Microbial Sensitivity TestsABSTRACT
Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide the first preclinical evidence demonstrating that although diet-induced acute zinc deficiency (Zn-D: ~50% decrease) did not worsen infection induced by either influenza A (H1N1) or methicillin-resistant staph aureus (MRSA), Zn-D mice were sensitive to the injurious effects of superinfection of H1N1 with MRSA. Although the mechanism underlying the sensitivity of ZnD mice to combined H1N1/MRSA infection is unclear, it was noteworthy that this combination exacerbated lung injury as shown by lung epithelial injury markers (increased BAL protein) and decreased genes related to epithelial integrity in Zn-D mice (surfactant protein C and secretoglobins family 1A member 1). As bacterial pneumonia accounts for 25%-50% of morbidity and mortality from influenza A infection, zinc deficiency may be an important pathology component of respiratory tract infections.
Subject(s)
Influenza A Virus, H1N1 Subtype , Malnutrition , Methicillin-Resistant Staphylococcus aureus , Pneumonia, Bacterial , Animals , Mice , Pneumonia, Bacterial/complications , Staphylococcus aureus , ZincABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis Radix (PR) is a traditional herbal remedy used to prevent and treat lung inflammation, and platycodins are speculated to be the major active constituents. However, concrete experimental verification for this assertion remains absent thus far. AIM OF THE STUDY: This study aims to compare the pulmonary distribution dynamics of five platycodins and analyze their effects on cytokines. Through the grey relational analysis (GRA) between pulmonary active components and cytokines, the study ascertains platycodins as the potential effective component against lung inflammation. MATERIALS AND METHODS: A rat lung inflammation model was created using lipopolysaccharides (LPS). Pulmonary distribution dynamics were analyzed via LC-MS/MS. Cytokine changes and distribution patterns in lung tissues were studied by multi-factor reagent kit. GRA was applied to determine correlations between pulmonary components and cytokines. Finally, the anti-inflammatory properties of platycodins were further studied using LPS-induced BEAS-2B cells in vitro. RESULTS: The results showed that five platycodins (Platycodin D, Platycodin D3, Deapio Platycodin D, 3-O-ß-D-Glucopyranosyl Platycodigenin, and Platycodigenin) featured fast absorption rate, short time to peak, and slow metabolism rate. The pulmonary distribution dynamics were significantly affected within 2 h after LPS modeling. At the same time, PR altered the relationships among different cytokines induced by LPS stimulation, particularly inflammatory cytokines IL-6 and IFN-γ. The GRA results indicated good correlation between the pulmonary distribution dynamics of the five platycodins components and the changing patterns of cytokine levels, with Platycodin D3 contributing the most. Additionally, Platycodin D3 exhibited a protective role against LPS-induced inflammation by reducing the production of pro-inflammatory mediators such as IL-1ß, IL-8, and ROS, as well as increasing the expression of the anti-inflammatory mediator IL-10. CONCLUSIONS: Platycodins are the main anti-inflammatory agents in PR and there is a good correlation with cytokines. This contributes to the anti-pneumonia effect of PR.
Subject(s)
Cytokines , Pneumonia , Saponins , Triterpenes , Rats , Animals , Cytokines/metabolism , Chromatography, Liquid , Lipopolysaccharides/pharmacology , Tandem Mass Spectrometry , Lung , Pneumonia/chemically induced , Pneumonia/drug therapy , Pneumonia/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Qingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J. Ellis, Platycodon grandiflorus (Jacq.) A. DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional Chinese medicinal formula, QJHTT has been used for more than 400 years in China. It has shown promising results in treating influenza A virus (IAV) pneumonia. AIM OF THE STUDY: To elusive the specific pharmacological constituents and mechanisms underlying its anti-IAV pneumonia effects. MATERIALS AND METHODS: The components in QJHTT were analyzed through the use of a serum pharmacology-based ultra high-performance liquid chromatography Q- Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) method. Simultaneously, the dynamic changes in IAV-infected mouse lung viral load, lung index, and expression of lung inflammation factors were monitored by qRT-PCR. RESULTS: We successfully identified 152 chemical components within QJHTT, along with 59 absorbed chemical prototype constituents found in the serum of mice treated with QJHTT. 43.45% of these chemical components and 43.10% of the prototype constituents were derived from the monarch drugs, namely Huangqin and Zhizi, aligning perfectly with traditional Chinese medicine theory. Notably, our analysis led to the discovery of 14 compounds within QJHTT for the first time, three of which were absorbed into the bloodstream. Simultaneously, we observed that QJHTT not only reduced the viral load but also modulated the expression of inflammation factors in the lung tissue including TNF-α, IL-1ß, IL-4, IL-6, IFN-γ, and IL17A. A time-effect analysis further revealed that QJHTT intervention effectively suppressed the peak of inflammatory responses, demonstrating a robust anti-IAV pneumonia effect. CONCLUSIONS: We comprehensively analyzed the pharmacological material basis of QJHTT by a highly sensitive and high-resolution UHPLC-Q Exactive Orbitrap-MS method, and demonstrated its efficacy in combating IAV pneumonia by reducing lung viral load and inflammatory factors. This study has significant importance for elucidating the pharmacological basis and pharmacological mechanism of QJHTT in combating IAV pneumonia.
Subject(s)
Drugs, Chinese Herbal , Plants, Medicinal , Pneumonia, Viral , Mice , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Lung , Pneumonia, Viral/drug therapy , Plants, Medicinal/chemistry , Antibodies , Chromatography, High Pressure Liquid/methodsABSTRACT
As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Subject(s)
COVID-19 , Humans , Medicine, Chinese Traditional , SARS-CoV-2 , Critical Illness , Treatment OutcomeABSTRACT
BACKGROUND: This study aimed to assess the knowledge, attitudes, and practices (KAP) of the general population to community-acquired pneumonia (CAP) and COVID-19. METHODS: A cross-sectional study was conducted between September 2022 and February 2023, involving the general population from Ningbo Municipal Hospital of Traditional Chinese Medicine with a self-developed questionnaire. RESULTS: A total of 637 valid questionnaires were collected, with the majority of participants being female (62.48%). The mean score for knowledge, attitudes, and practices were 7.60 ± 2.39 (possible range: 0-12), 43.20 ± 4.57 (possible range: 11-55), and 34.57 ± 4.95 (possible range: 10-50), respectively. Multivariate logistic regression analysis indicated that master's degree or above (OR = 6.04, 95% CI: 1.80-20.31, P = 0.004) and occupation in business or service careers (OR = 0.28, 95% CI: 0.17-0.48, P < 0.001) were independent associated with knowledge. The knowledge (OR = 1.32, 95%CI: 1.20-1.44, P < 0.001) and female gender (OR = 1.48, 95%CI: 1.03-2.14, P = 0.036) were independently associated with positive attitudes. Attitudes (OR = 1.34, 95%CI: 1.26-1.43, P < 0.001) and a monthly household income greater than 20,000 RMB (OR = 0.31, 95%CI: 0.15-0.64, P = 0.001) were independent associated with practices. Pearson correlation analysis revealed that knowledge positively correlated with attitude scores (r = 0.348, P < 0.001) and practice scores (r = 0.259, P < 0.001), and attitude and practice scores were also positively correlated (r = 0.563, P < 0.001). Structural equation modeling showed that knowledge predicted attitudes (ß = 0.67, P < 0.001) and practices (ß = 0.17, P = 0.017), while attitudes predicted practices (ß = 0.58, P < 0.001). CONCLUSION: General population had moderate knowledge, positive attitudes and average practices towards CAP and COVID-19.
Subject(s)
COVID-19 , Humans , Female , Male , COVID-19/epidemiology , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Surveys and Questionnaires , OccupationsABSTRACT
Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.
Subject(s)
COVID-19 , Methemoglobinemia , Female , Humans , Methemoglobinemia/chemically induced , Methemoglobinemia/diagnosis , Methemoglobin , Dapsone/adverse effects , OxygenABSTRACT
Perillaldehyde is a monoterpene compound mainly from the medicinal plant Perilla frutescens (L.) Britt., which has hypolipidemic, antioxidant, antibacterial and anti-inflammatory functions. In this investigation, we discovered that Perillaldehyde had powerful antimicrobial activity against Acinetobacter baumannii 5F1, and its minimum inhibitory concentration was 287.08 µg/mL. A. baumannii is a conditionally pathogenic bacterium with a high clinical resistance rate and is a major source of hospital infections, especially in intensive care units, which is one of the main causes of pneumonia. Inflammatory immune response is characteristic of pneumonia caused by A. baumannii infection. The results of our in vitro experiments indicate that Perillaldehyde disrupts the cell membrane of A. baumannii 5F1 and inhibits its quorum sensing to inhibit biofilm formation, among other effects. With an experimental model of murine pneumonia, we investigated that Perillaldehyde decreased NLRP3 inflammasome activation and TNF-α expression in lung tissues by inhibiting the NF-κB pathway, and also impacted MAPKs protein signaling pathway through the activation of TLR4. Notably, the use of high doses of Perillaldehyde for the treatment of pneumonia caused by A. baumannii 5F1 infection resulted in a survival rate of up to 80 % in mice. In summary, we demonstrated that Perillaldehyde is promising as a new drug for the treatment of pneumonia caused by A. baumannii 5F1 infection.
Subject(s)
Acinetobacter baumannii , Pneumonia , Mice , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Monoterpenes/pharmacology , Monoterpenes/therapeutic useABSTRACT
The significance of Vitamin D has been appreciated beyond bone health and calcium metabolism. The importance of Vitamin D in respiratory health has been recognized due to its immunomodulatory and anti-microbial properties. The hypothesis is that Vitamin D could have a significant role in the pathogenesis of respiratory diseases and may represent a novel preventive and therapeutic strategy. Furthermore, enumerable observational studies established the association of Vitamin D deficiency with respiratory diseases such as asthma, bronchiolitis, pneumonia, tuberculosis, etc. However, experimental studies have not shown the encouraging results. This brief review will summarize and discuss the synthesis and metabolism of Vitamin D, the prevalence of Vitamin D deficiency in children, its role in the pathogenesis of various childhood respiratory diseases, and an overview of the therapeutic trials assessing the role of Vitamin D supplementation in childhood respiratory diseases.
Subject(s)
Pneumonia , Respiration Disorders , Vitamin D Deficiency , Child , Humans , Vitamin D/therapeutic use , Respiration Disorders/complications , Respiration Disorders/drug therapy , Vitamins/therapeutic use , Pneumonia/drug therapy , Vitamin D Deficiency/epidemiology , Dietary SupplementsABSTRACT
Mycobacterium abscessus is a fast-growing non-tuberculous mycobacteria complex causing pulmonary infections, comprising the subspecies abscessus, massiliense and bolletii. Differences are based predominantly on natural inducible macrolide resistance, active in most Mycobacterium abscessus spp abscessus species and in Mycobacterium abscessus spp bolletii but inactive in Mycobacterium abscessus spp massiliense. Therapy consists in long-term treatment, combining multiple antibiotics. Prognosis is poor, as only 40% of patients experience cure. Pharmacodynamic and pharmacokinetic data on M. abscessus have recently been published, showing that therapy ineffectiveness might be explained by intrinsic bacterial resistance (macrolides ) and by the unfavorable pharmacokinetics of the recommended antibiotics. Other molecules and inhaled antibiotics are promising.