Exploring the mechanism of action of Shuangyang houbitong granules in the treatment of acute pharyngitis based on network pharmacology and molecular docking.

BACKGROUND: Acute pharyngitis (AP) refers to the acute inflammation of the pharynx, characterized by swelling and pain in the throat. Shuangyang houbitong granules (SHG), a traditional Chinese medicine compound, have been found to be effective in providing relief from symptoms associated with AP. METHODS: The chemical components of SHG were screened using Traditional Chinese Medicine Systems Pharmacology database, HERB database, and China National Knowledge Infrastructure. The targets of the granules were predicted using SwissTargetPrediction database. A network was constructed based on the targets of AP obtained from Genecards database, and protein-protein interaction analysis was performed on the intersection targets using STRING database. Key targets were screened for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and the binding activity of components and targets was predicted using AutoDockTools-1.5.7. RESULTS: A total of 65 components of SHG that met the screening criteria were retrieved, resulting in 867 corresponding targets. Additionally, 1086 AP target genes were retrieved, and 272 gene targets were obtained from the intersection as potential targets for SHG in the treatment of AP. Molecular docking results showed that the core components genkwanin, acacetin, apigenin, quercetin can stably bind to the core targets glyceraldehyde 3-phosphate dehydrogenase, interleukin 6, tumor necrosis factor, serine/threonine protein kinase, tumor protein 53, and epidermal growth factor receptor. CONCLUSION: The research results preliminarily predict and verify the mechanism of action of SHG in the treatment of AP, providing insights for further in-depth research.

Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

[Clinical comprehensive evaluation of Houyanqing Oral Liquid in treatment of acute pharyngitis].

This study systematically combed the existing evidence of Houyanqing Oral Liquid in the treatment of acute pharyngitis from the "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) and carried out qualitative and quantitative analysis of the data from each dimension. The multi-criteria decision analysis(MCDA) model and CSC v2.0 were used to evaluate the clinical value of this drug, so as to provide evidence for the selection of essential drugs in the department of otolaryngology and for medical and health decision-making. The dimensions are graded A, B, C, or D. The adverse reactions of Houyanqing Oral Liquid in the treatment of acute pharyngitis were mainly manifested as abdominal pain, diarrhea, rash, etc., which were relieved after drug withdrawal. In terms of safety, it was considered that Houyanqing Oral Liquid had controllable risk and high safety, which was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol can significantly improve the total response rate, shorten the time to abatement of fever and di-sappearance of throat pain and mucosal congestion, and alleviate mucosal congestion and cough with sputum. With medium-quality evidence, the effectiveness was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol had cost-effectiveness advantages in the treatment of acute pharyngitis, and its economy was rated as grade C with the evidence of general quality. For acute pharyngitis, Houyanqing Oral Liquid can shorten the disease course and obviously relieve sore throat. Moreover, it can be used for the treatment of radioactive pharyngitis and oral ulcer, and thus its innovation was rated as grade B. With convenient and simple administration and standard and complete drug information, the suitability of this drug was rated as grade B. Houyanqing Oral Liquid is derived from the folk prescription in Hunan province and has been subjected to real-world studies, and thus the TCM characteristics was rated as grade B. According to the ratings of all the dimensions, the comprehensive value of Houyanqing Oral Liquid in the clinical treatment of acute pharyngitis was determined as grade B, with sufficient evidence and clear results. It is suggested that the results should be conditionally converted into relevant policy of clinical basic drug management according to procedures.

Integrated metabolome-microbiome analysis investigates the different regulations of Pudilan Xiaoyan oral liquid in young rats with acute pharyngitis compared to adult rats.

BACKGROUND: Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases of the respiratory tract in children and adults. However, the endogenous changes in children and adults with PDL in the treatment of acute pharyngitis remain unclear. PURPOSE: The differential regulatory roles of PDL in endogenous metabolism and gut microbes in young and adult rats were investigated with a view to providing a preclinical data reference for PDL in medication for children. METHODS: An acute pharyngitis model was established, and serum levels of inflammatory factors and histopathology were measured. This study simulated the growth and development of children in young rats and explored the endogenous metabolic characteristics and intestinal microbial composition after the intervention of PDL by using serum metabolomic technique and 16S rRNA high-throughput sequencing technique. RESULTS: The results showed that PDL had therapeutic effects on young and adult rats with acute pharyngitis. Sixteen biomarkers were identified by metabolomics in the serum of young rats and 23 in adult rats. PDL can also affect intestinal microbial diversity and community richness in young and adult rats. Alloprevotella, Allobaculum, Alistipes, Bifidobacterium, and Enterorhabdus were prominent bacteria in young rats. Bacteria from the phylum Firmicutes of the adult rats changed more significantly under the treatment of PDL. In young rats, amino acid metabolism was the primary regulatory mode of PDL, whereas, in adult rats, glycerophospholipid metabolism was studied. CONCLUSION: The regulation of PDL on the serum metabolite group and intestinal microflora in young rats was different from that in adult rats, indicating the necessity of an independent study on children's medication. PDL may also exert therapeutic effects on young and adult rats by regulating gut microbial homeostasis. The results support the clinical application of PDL.

[Clinical comprehensive evaluation of Jinsang Liyan Pills/Capsules in treatment of chronic pharyngitis].

According to the Guidelines for clinical comprehensive evaluation of Chinese patent medicine(2022 version), this study comprehensively compared the clinical value of Jinsang Liyan Pills/Capsules with that of another commonly used Chinese patent medicine(drug A).(1)Effectiveness: Jinsang Liyan Pills/Capsules had antimicrobial, anti-inflammatory, and pain-relieving effects and can improve the total response rate in the treatment of chronic pharyngitis. Moreover, they took effect faster than the control group.(2)Safety: Jinsang Liyan Pills/Capsules did not cause acute toxicity and long-term toxicity, with low incidence of adverse reactions, which were mild and alleviated after drug withdrawal. Therefore, the risk of Jinsang Liyan Pills/Capsules was under control.(3)Economy: Jinsang Liyan Pills/Capsules had lower cost per course of treatment than drug A. The incremental cost-effectiveness ratio(ICER) of Jinsang Liyan Pills combined with Jinsang Qingyin Pills was-39.97 yuan compared with conventional treatment. The ICER of Jinsang Liyan Pills compared with amoxicilin was 0.01 yuan. The results meant that Jinsang Liyan Pills/Capsules had a cost-effectiveness advantage.(4)Innovation: Jinsang Liyan Pills/Capsules had reasonably formula and wide indications, meeting the clinical needs. Moreover, they had been authorized four patents of advanced manufacturing technology.(5)Suitability: the storage and administration of Jinsang Liyan Pills/Capsules were convenient, with clear instruction of medication.(6) Accessibility: Jinsang Liyan Pills/Capsules had sufficient drug reserve, caused low economic burden of patients, and presented environmental bearing capacity. Finally, Jinsang Liyan Pills/Capsules were scored 79.10 points, and drug A 67.93 points. The experts reached the consensus of grade A for Jinsang Liyan Pills/Capsules, which can be directly converted into decision making. The result of this comprehensive evaluation of Jinsang Liyan Pills/Capsules highlight the clinical advantages in the treatment of chronic pharyngitis and lay a foundation for the standardized research on the clinical basic research of the drug in the future.

[Systematic review and Meta-analysis of Lianhua Qingwen preparations combined with Oseltamivir in treatment of influenza].

This study aims to explore the efficacy and safety of Lianhua Qingwen preparations combined with Oseltamivir in the treatment of influenza patients. PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang, and VIP were searched for the randomized controlled trials(RCTs) involving the comparison between the influenza patients treated with Lianhua Qingwen preparations combined with Oseltamivir and those treated with Oseltamivir alone. Fever clearance time was taken as the primary outcome indicator. Clinical effective rate(markedly effective and effective), time to muscle pain relief, time to sore throat relief, time to cough relief, time to nasal congestion and runny nose relief, time to negative result of viral nucleic acid test, and adverse reactions were taken as the secondary outcome indicators. The data were extracted based on the outcome indicators and then combined. The Cochrane collaboration's tool for assessing risk of bias was used to evaluate the quality of a single RCT, and the grading of recommendations assessment, development and evaluations(GRADE) system to assess the quality of a single outcome indicator. RevMan 5.3 was employed to analyze data and test heterogeneity. Finally, 16 RCTs involving 1 629 patients were included for analysis. The Meta-analysis showed that Lianhua Qingwen preparations combined with Oseltamivir was superior to Oseltamivir alone in the treatment of influenza in terms of clinical effective rate(RR=1.16, 95%CI [1.12, 1.20], P<0.000 01), fever clearance time(SMD=-2.02, 95%CI [-2.62,-1.41], P<0.000 01), time to muscle pain relief(SMD=-2.50, 95%CI [-3.84,-1.16], P=0.000 2), time to sore throat relief(SMD=-1.40, 95%CI [-1.93,-0.85], P<0.000 01), time to cough relief(SMD=-1.81, 95%CI [-2.44,-1.19], P<0.000 01), time to nasal congestion and runny nose(SMD=-2.31, 95%CI [-3.61,-1.01], P=0.000 5), and time to negative result of viral nucleic acid test(SMD=-0.68, 95%CI [-1.19,-0.16], P=0.01). However, due to the low quality of the trials, the above conclusions need to be proved by more high-quality clinical studies. In addition, we still need to attach importance to the adverse reactions of the integrated application of Chinese and western medicines.

Adverse events of biological therapy in chronic rhinosinusitis with nasal polyps: A systematic review.

The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment modalities impact the quality of patients' lives. Monoclonal antibody treatment has recently been used successfully in CRS with limited reported adverse events. We aimed to review the literature to shed more light on the safety and adverse events associated with the biological therapy of CRSwNP. A comprehensive systematic review was conducted on the safety of different biological treatments when used for managing CRSwNP. We have included 13 studies in the present systematic review, including 12 randomized controlled trials (RCTs) and one cross-sectional study. The total sample size for the included studies was 2282 patients. Six studies investigated the safety and adverse events of dupilumab; three investigated omalizumab, three investigated mepolizumab, and only one investigated reslizumab. Some studies have reported that adverse events were common with these types of drugs. However they were not specific and self-limited. Headaches, injection site reactions, and pharyngitis were the most common adverse events found among the reported adverse events. The Dupilumab trial reported pharyngitis in 225 patients (22.4 %) followed by erythema in 9.4 %, headache in 8.1 %, epistaxis in 5.1 %, and asthma in 1.7 % of patients. Trials which used omalizumab reported headaches, nasal pharyngitis, injection-site reactions to be the most common adverse events with estimated prevalence rates of 8.1 %, 5.9 %, and 5.2 %, respectively. Mepolizumab and reslizumab studies reported that 40 % of patients were complicated by nasal polyps/congestion/pharyngitis/infections, 14 had a headache (15.5 %), two developed asthma (2.2 %), and only one patient (1.1 %) had epistaxis as an adverse event. Although the literature's current investigations indicate the safety of the biologic treatment modalities, further studies are needed as some uncertainty among the trials have been reported.

Kikyo-to for Acute Upper Respiratory Tract Infection-Associated Sore Throat Pain: A Multicenter Randomized Controlled Trial.

Objectives: Kikyo-to (Kt), a herbal medicine composed of glycyrrhiza root (Chinese licorice) and Platycodon root extracts (Chinese bellflower), is commonly used in Japan for relief of throat symptoms related to acute upper respiratory tract infection (URTI). Its effectiveness on URTI-associated sore throat pain over 30 min is examined here in comparison with a placebo. Design: Randomized double-blinded multicenter trial. Settings/Location: Two local Japanese medical centers with primary care. Subjects: Patients aged 20-65 years with URTI-related sore throat. Interventions: Patients were randomized to receive either 2500 mg of Kt, or 2500 mg of placebo (lactose). Randomization was stratified by age (< 45 vs. ≥ 45 years) and baseline sore throat score according to visual analogue scale (VAS) (< 50 vs. ≥ 50). Outcome measures: Primary outcome was change to sore throat score according to VAS 30 min after administration of Kt. Perceived impact of the sore throat on daily life at 30 mins after administration was another outcome. Outcomes are analyzed in the intention-to-treat population. Results: Among 70 participants, (Kt group: 36; placebo group: 34), each group contained 34 patients for analysis (n = 68, total). Difference between the groups in the mean change of sore throat score according to VAS at 30 min was without statistical significance (Kt 15.3, placebo 17.2; p = 0.66). Patients reporting that their sore throat had a moderate or greater impact on daily life were also similar in proportion between the groups (Kt 61.8% vs. placebo 55.9%; p = 0.80). Side effects were not reported. Conclusions: Kt did not relieve acute URTI-associated sore throats significantly more than a placebo. (UMIN trial ID: UMIN000035591).

Network Pharmacological Analysis and Experimental Study of the Antipharyngitis Mechanism of the Chaiqin Qingning Capsule.

Objective: The study aimed to explore the active composition and mechanism of the Chaiqin Qingning capsule (CQQN) against pharyngitis based on the network pharmacology and through using a pharyngitis rat model. Methods: The active ingredients and targets of CQQN were queried using the TCMSP database. Disease-related target genes were queried in the DrugBank, GeneCards, OMIM, and DisGeNEt databases using "pharyngitis" as the search term. The STRING database was used to establish a protein-protein interaction (PPI) network. GO function enrichment and KEGG pathway enrichment analyses were performed to identify active components and key targets. Cytoscape software (version 3.7.2) was used to construct an active component/target gene/enrichment pathway network. AutoDock software was used to select the best binding target for molecular docking. The effect of CQQN was verified in the pharyngitis rats. Results: Network pharmacology showed 30 active compounds in CQQN with 240 targets, including 54 for the treatment of pharyngitis. Potential active ingredients included quercetin, kaempferol, stigmasterol, saikosaponin D, and isorhamnetin. The key targets involved were AKT1, TNF, IL-6, and IL-1ß. Signaling pathways included virus infection, TNF, IL-17, and cancer pathways. The molecular docking results showed that the critical components in CQQN had good potential for binding to key target genes. Animal experiments showed that CQQN could significantly reduce the expression of TNF-α, IL-1ß, IL-6, and IL-17 in the serum of rats with pharyngitis (P < 0.05). Hematoxylin and eosin staining showed that the inflammatory state of pharyngeal tissue in rats was significantly reduced compared to that in the model group. Conclusion: CQQN can improve pharyngitis by regulating the TNF and IL-17 signaling pathways. The study makes a positive exploration and provides a new idea for a more comprehensive and in-depth excavation of CQQN with an intervention effect on pharyngitis and other upper respiratory diseases in the future.

[Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia].

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1ß(IL-1ß), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor ß1(TGF-ß1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1ß, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

[Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients].

OBJECTIVE: To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat). METHODS: With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups. RESULTS: A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001). CONCLUSION: Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.

Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.

In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1ß, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.

Elucidation of the mechanism of action of Runyan Mixture in the treatment of pharyngitis using a network pharmacological approach.

This study aimed to elucidate the mechanism of action of Runyan Mixture in treating pharyngitis using a network pharmacological approach. The active components of the Runyan Mixture were obtained from the traditional chinese medicine systems pharmacology database and evaluated using Lipinski's rules. The SwissTargetPrediction database was used to predict the action targets of the Runyan Mixture, and a protein-protein interaction network was constructed using the STRING database. Moreover, the anti-inflammatory effect of Runyan Mixture was validated in vitro using the lipopolysaccharide induced inflammation in macrophages. The Runyan Mixture was the liquid preparation from 8 traditional Chinese medicine. A total of 89 types of active components, 53 core targets, and 98 signaling pathways (P < .001) were identified for the Runyan Mixture. The main action targets were EGFR, MAPK1, AKT1, PIK3CA, NFKB1, SRC, TNF, MAPK8, MET, and PTGS2. Among the identified signaling pathways, 20 were associated with microbial infection and 24 were related to the immune-inflammatory response. Experimental results in vitro showed that Runyan Mixture could significantly inhibit the expression of interleukin-1, interleukin-6, and tumor necrosis factor-α (P < .05) in macrophages by lipopolysaccharide stimulation. Based on the results of the protein-protein interaction network analysis and the anti-inflammatory effect in vitro, the efficiency of the Runyan Mixture in pharyngitis treatment could be attributed to the inhibition of the inflammatory response.

Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients / 中国针灸

OBJECTIVE@#To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat).@*METHODS@#With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups.@*RESULTS@#A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001).@*CONCLUSION@#Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.

Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia / 中国中药杂志

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

Mechanism of Yinqin Oral Liquid in the Treatment of Chronic Pharyngitis Based on Network Pharmacology.

BACKGROUND: Yinqin oral liquid (YOL) has curative effect for upper respiratory tract infections, especially for chronic pharyngitis (CP). Since the traditional Chinese herbal formulae are complicated, the pharmacological mechanism of YOL remains unclear. The aim of this work was to explore the active ingredients and mechanisms of YOL against CP. METHODS: First, the profile of putative target of YOL was predicted based on structural and functional similarities of all available YOL components, which were obtained from the Drug Bank database, to the known drugs using TCMSP. The chemical constituents and targets of honeysuckle, scutellaria, bupleurum and cicada were searched by TCMSP, CTD, GeneCards and other databases were used to query the CP-related genes, which were searched by UniProt database. Thereafter, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. RESULTS: The pathway enrichment analysis showed 55 compounds and 113 corresponding targets in the compound-target network, and the key targets involved PTGS1, ESR2, GSK3ß, NCOA2, ESR1. The PPI core network contained 30 proteins, including VEGFA, IL6, ESR1, RELA and HIF1A. A total of 148 GO items were obtained (p<0.05), 102 entries on biological process (BP), 34 entries on biological process (BP) and 12 entries on cell composition (CC) were included. A total of 46 signaling pathways were obtained by KEGG pathway enrichment screening (p<0.05), involving cancer, PI3K-AKT, hepatitis, proteoglycans, p53, HIF-1 signaling pathways. CONCLUSION: These results collectively indicate YOL (including the main ingredients luteolin and baicalein) as a highly effective therapeutic agent for anti-inflammation, through the NF-kB pathway.

Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment.

PURPOSE: This study aimed to investigate the molecular mechanisms of compound herba Sarcandrae aerosol, also known as the Fufang Zhongjiefeng (FFZJF) aerosol, in treating chronic pharyngitis (CP) using network pharmacology and in vivo experimental approaches. METHODS: Active compounds and putative targets of five herbs in FFZJF were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction databases. The therapeutic targets of CP were obtained from OMIM, Durgbank, DisGeNT, and GAD databases. The active compounds-target networks were constructed using Cytoscape 3.6.1. The overlapping targets of FFZJF active compounds and CP targets were further analyzed using the String database to construct protein-protein interaction (PPI) network. KEGG pathway and Gene Ontology enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. The predicted targets and pathways were validated in a group A ß-hemolytic streptococcus-induced rat CP model. RESULTS: There were 45 active compounds identified from FFZJF and 11 potential protein targets identified for CP treatment. PPI network demonstrated that IL6, PTGS2, TLR-4, and TNF may serve as the key targets of FFZJF for the treatment of CP. The main functional pathways involving these key targets include cytokine secretion, inflammatory response, MyD88-dependent toll-like receptor signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. In a rat CP model, the elevation of serum TNF-α, IL1ß, and IL6 levels, as well as the upregulation of TLR-4, MyD88, NF-κB P65 in the pharyngeal mucosal tissues could be effectively reduced by FFZJF treatment in a dose-dependent manner. CONCLUSION: Through a network pharmacology approach and animal study, we predicted and validated the active compounds of FFZJF and their potential targets for CP treatment. The results suggest that FFZJF can markedly alleviate GAS-induced chronic pharyngitis by modulating the TLR-4/MyD88/NF-κB signaling pathways.

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

OBJECTIVE: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity. METHODS: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. RESULTS: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1ß (P＜0.05), IL-6 (p＜0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract. CONCLUSIONS: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.

Antibacterial, anti-inflammatory and antioxidant activities of Mahanintangtong and its constituent herbs, a formula used in Thai traditional medicine for treating pharyngitis.

BACKGROUND: Mahanintangtong is listed in the Thailand's National List of Essential Medicines (NLEM). It is used to treat non-specific fevers and illnesses such as pharyngitis and chickenpox. In this study, we investigated the biological activities of the different medicinal plants used in the Mahanintangtong formula. METHODS: The plant materials were extracted by maceration and decoction. Antimicrobial activity, assessed by disc diffusion method, the minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were compared with commercially available standard antibiotics. To elucidate the anti-inflammatory mechanisms, inhibition of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) production was tested by Griess and ELISA techniques. Antioxidant activity was measured by ABTS and DPPH scavenging assays. RESULTS: The extracts with the best antimicrobial activities were carbonized Tectona grandis showing against Streptococcus pyogenes, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The ethanol extract of Dracaena loureiroi wood exhibited the highest NO and IL-6 inhibitory activity with IC50 values of 9.42 ± 1.81 and 12.02 ± 0.30 µg/mL, respectively. The ethanol extract of Pogostemon cablin had the highest TNF-α inhibitory with IC50 values of 10.68 ± 0.02 µg/mL. In anti-free radical testing, the ethanol extract of D. loureiroi displayed high antioxidant activity by both ABTS and DPPH assays. CONCLUSION: The ethanol extracts from carbonized T. grandis and Mahanintangtong showed good antimicrobial activity, especially against S. pyogenes, and good anti-inflammatory activity. These findings are relevant to the pathogenesis of pharyngitis and justify additional studies to see if Mahanintangtong could have clinical utility.

Evaluation on immediate analgesic efficacy and safety of Kai-Hou-Jian spray (children's type) in treating sore throat caused by acute pharyngitis and tonsillitis in children: study protocol for a randomized controlled trial.

BACKGROUND: Acute pharyngitis and tonsillitis are common respiratory diseases for which children seek medical care. Their main clinical manifestation is sore throat which interferes with patients' quality of life. However, there is no proven effective or safe method to treat it. It is necessary to find an excellent strategy to reduce sore throat and reduce the burden of acute illness. We designed the randomized controlled trial with the characteristics of traditional Chinese medicine (TCM) to determine the clinical positioning of Kai-Hou-Jian spray (children's type) (KHJS) through evidence-based research. This trial aims to evaluate the immediate analgesic efficacy of KHJS on sore throat caused by acute pharyngitis and tonsillitis (wind-heat syndrome/heat exuberance in lung and stomach syndrome) in children and to observe its safety. METHODS/DESIGN: This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. It will include 240 children with acute pharyngitis/tonsillitis from 7 study sites across China. All participants are randomly assigned to two parallel treatment groups, one with KHJS and the other with placebo sprays, for 5 consecutive days. The primary outcome is the time of analgesic onset. Secondary outcomes include duration of analgesic effect, area under time curve of 0-3 h Wong-Baker FACES Pain Rating Scale (WBS) score (AUC0-3 h), rate of analgesic onset, rate of disappearance of sore throat, changes of WBS score (in days), effective rate of pharyngeal signs, and effective rate of TCM syndrome. The incidence of adverse events during the trial is the primary safety outcome. In addition, vital signs and laboratory tests before and after medication are monitored. DISCUSSION: To our knowledge, this will be the first clinical trial to explore the immediate analgesic efficacy of a Chinese patent medicine spray for acute pharyngitis/tonsillitis induced sore throat in children in a multicenter, randomized, double-blinded, parallel-group, placebo-controlled manner. Not only might it prove the efficacy and safety of KHJS in the treatment of sore throat caused by acute pharyngitis/tonsillitis in children, but it might also provide evidence for the treatment of acute sore throat with Chinese herbal medicine. TRIAL REGISTRATION: A multicenter, randomized, double-blind, very low-dose, parallel controlled trial for the immediate analgesic effect and safety of Kai-Hou- Jian spray (children's type) in the treatment of sore throat caused by acute pharyngitis and tonsillitis in children. Chinese Clinical Trial Registry ChiCTR2000031599 . Registered on 5 April 2020.