lianhua qingwen contraindication

Cytokine storm is an excessive immune response of the body to external stimuli such as viruses, which will stimulate the secretion of a large number of inflammatory factors and lead to cytokine cascade reaction [4,6]. For pooled studies, the incidence of adverse reactions was lower in the LHQW group than the conventional drug group (RR = 0.63, 95% CI = 0.580.69, p < 0.001). Systematic Review Registration: https://clinicaltrials.gov/, CRD-42020224180. sharing sensitive information, make sure youre on a federal (Yuxingcao), Pogostemon cablin (Blanco) Benth. Objectives: Lianhua Qingwen capsule/granule (LHQW) is an innovative patented traditional Chinese medicine with potential curative effects on respiratory diseases. Broad Anti-viral Capacities of Lian-Hua-Qing-Wen Capsule and Jin-Hua-Qing-gan Granule and Rational Use against Covid-19 Based on Literature Mining. Additionally, LHQW group also had shorter time to recovery of fever, fatigue and coughing, and higher improvement rate in chest computed tomographic manifestations and clinical cure [43]. On March 27, 2019, Yiling Pharmaceutical Co. Ltd. amended the LHQW drug manual to include adverse reactions related to its clinical application. recently published a clinical study on the treatment of mild COVID-19 with LHQW granules (6g, tid) combined with abidor (0.2g, tid) [44]. 48 (3), 737762. For rheum, sample size could partially explain heterogeneity (p = 0.005), but not year of publication (p = 0.658) and treatment of the control group (p = 0.712). LQ15H280003), the Clinical Research Projects of Zhejiang Medical Association (No. Li H.R., Chang L.P., Wei C., Jia Z.H. Furthermore, we also found that LHQW group has a reduced incidence of respiratory system damage compared to the conventional drug group. Ther. There was no statistically significant difference in the incidence of adverse reactions during treatment of herpes zoster between the LHQW group and the conventional drug group (RR = 0.80, 95% CI = 0.521.23, p = 0.302). Seven studies reported the adverse reactions of hepatobiliary system damage. [8] A January 2022 meta-analysis from China reports that it may cause GI discomfort, rashes and itches, dry mouth, and dizziness, but emphasizes that the effects are more common with "conventional treatment". Meanwhile, the network pharmacology analysis confirmed that its effects were mainly focused on the biological processes such as the response to LPS, the molecular response to bacterial origin, the response to metal ions and cell biological stimulation [41]. Further evaluation revealed that LHQW significantly inhibited SARS-CoV-2 replication in Vero E6 cells, markedly reduced pro-inflammatory cytokines (TNF-, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production and resulted in abnormal particle morphology of virion in cells [30]. Furthermore, they identified two important metabolites, prostaglandin F2 and arachidonic acid, and their arachidonic acid metabolism pathway, as vital indicators of LHQW in treating influenza by using serum metabolomics analysis [19]. Sci.). [7] In the United States, the FDA is advising consumers not to purchase or use Lianhua Qingwen, stating that it has not been approved or authorized by FDA and is being misleadingly represented as safe and/or effective for the treatment or prevention of COVID-19. School of Pharmacy, Faculty of Life Sciences, University College London, United Kingdom. Efficacy and safety of Lianhua Qingwen capsule for influenza: a systematic review. Identification of a pharmacological biomarker for the bioassay-based quality control of a thirteen-component TCM formula (Lianhua Qingwen) used in treating influenza A virus (H1N1) infection. Lianhua Qingwen(Forsythia suspensa (Thunb.) LHQW, an innovative proprietary traditional Chinese medicine used to treat influenza, was approved by the Food and Drug Administration of the United States for Phase II of clinical trial in 2015 (Ye et al., 2020). Z., Wang, H. T., Han, X., Liu, C., Sun, Y. N., Liu, B., et al. Hu K., Guan W.J., Bi Y., Zhang W., Li L., Zhang B., Liu Q., Song Y., Li X., Duan Z., Zheng Q., Yang Z., Liang J., Han M., Ruan L., Wu C., Zhang Y., Jia Z.H., Zhong N.S. Management of adverse reactions was clearly documented in 38 studies, which reported improvement or resolution through discontinuation of medication, changes to post-meal administration, symptomatic or no treatment. LYY19H280006, No. The https:// ensures that you are connecting to the Methods and analysis : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the . Careers, Unable to load your collection due to an error. The therapeutic effect of the traditional Chinese medicine Lianhua Qingwen in this new coronary pneumonia epidemic has attracted attention from all walks of life, and relevant research reports continue to appear. BMJ. Chin. The site is secure. Wang Z., Chen X., Lu Y., Chen F., Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and western medicine treatment. Since the outbreak of COVID-19, Lianhua Qingwen Capsules have been recommended by the official Chinese "Diagnosis and Treatment Protocol for COVID-19" and widely used in designated admission hospitals for COVID-19. [14] Retraction Watch also notes that author Jia Zheng-hua is the son-in-law of Wu Yi-ling, the founder of the company in question. Clinical Drug Safety of Lianhuaqingwen Preparation: a Systematic Evaluation. Some notable dangerous reactions include heart attacks, strokes, seizures, and sudden deaths. After 7 days of treatment, the main TCM syndrome scores (fever, fatigue, cough, dry throat, chest tightness), C-reactive protein and procalcitonin levels in the LHQW group were significantly lower, and the white blood cell and lymphocyte counts were obviously higher than those in abidor group [44]. Statistical analysis was performed with Stata 14 software (Stata Corporation, College Station, TX, USA). COPD is characterized by a chronic inflammatory response and can be worsened by acute exacerbations. 327 (7414), 557560. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. A total of 420 participants with influenza (ages from 18 years to 65 years) were randomly divided into three groups: high dose LHQW capsule treatment (6 capsules each time, bid), low dose LHQW capsule treatment (4 capsules of LHQW+2 capsules of placebo each time, bid) and placebo intervention (6 capsules of placebo each time, bid). As COVID-19 has led to serious death and lacks treatment strategies, the potential therapeutic drugs are increasingly being explored. doi:10.1111/j.0006-341x.2000.00455.x, Fan, Z., Guo, G., Che, X., Yang, Y., Liu, Y., Li, L., et al. Meta-analysis and systematic review of efficacy and safety of Lianhua Qingwen in adjuvant treatment of adult pneumonia. Otherwise, the fixed-effects model was used (DerSimonian and Laird, 1986; Higgins et al., 2003). CONTRAINDICATIONS Uncertainty. doi:10.1111/j.1365-2796.1990.tb00199.x, Higgins, J. P., Altman, D. G., Gtzsche, P. C., Jni, P., Moher, D., Oxman, A. D., et al. There was no statistically significant difference in the incidence of adverse reactions during treatment of viral influenza between the LHQW group and the conventional drug group (RR = 0.75, 95% CI = 0.471.21, p = 0.244). Percentage of risk of bias for all qualified studies. Trials. Data analysis were done by CH and DZ. FIGURE 1. COVID-19 has led to a great case fatality. Our meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (Moher et al., 2009), and registered with PROSPERO (CRD42020224180). 13 (08), 676681. 3.2.2. doi:10.26434/chemrxiv.12016236.v1. We examined 54 studies on treatment of influenza, 42 of which reported adverse reactions. During the study, no serious adverse events were reported. Herald. It may benefit the treatment of COVID-19 by the signaling pathways such as advanced glycation end products (AGE)-receptor of AGE (RAGE), TNF, sarcoma-associated herpesvirus infection, IL-17 and human cytomegalovirus infection [41]. vahl (weeping forsythia) fruit 27.41 mg, Lonicera japonica Thunb. Ma Y., Zhang Z., Wei L., He S., Deng X., Ji A., Zhou B., Jiang D., Li M., Wang Y. Efficacy and safety of Reduqing granules in the treatment of common cold with wind-heat syndrome: a randomized, double-blind, double-dummy, positive-controlled trial. Lu Z.J., Wu L.Y., Mou Y.Y., Duan H.M., Chen R.C., Xiao Y., Zheng W.J. Ping F., Li Z., Zhang F., Li D., Han S. Effects of Lianhua Qingwen on pulmonary oxidative lesions induced by fine particulates (PM2.5) in rats. Finally, all adverse reactions were described solely based on grouping of patients into treatment and control categories and no data were obtained according to gender stratification, which limited further analysis. government site. Rev. Lianhua Qingwen is a commonly used Chinese patent medicine to treat viral infection. Results: In total, 217 experimental studies were included. The Trim and Fill method was further applied to assess the impact of publication bias. Med. Royal Botanic Gardens, Kew science (2021). CFDA has recently approved adding a new indication for LHQW in mild and common COVID-19 patients, but whether it would bring benefits for the severe cases is unclear. Evid. Received 2020 Jul 3; Revised 2020 Aug 9; Accepted 2020 Aug 16. doi:10.13422/j.cnki.syfjx.20201099, Ye, C., Gao, M., Lin, W., Yu, K., Li, P., and Chen, G. (2020). Contraindications . Wang, Y., Greenhalgh, T., and Wardle, J. 339 (7), b2535. The literature materials were collected from the scientific databases including the Pubmed, CNKI and Web of Science (up to August 8, 2020), on ethnobotany and ethno medicines. Jiao Qu revised the manuscript. Lianhua Qingwen Capsules of Yiling Pharmaceutical Approved in mauritius. 26 (11), 812. In mice after infected with the flu virus FM1, LHQW capsule obviously increased IFN- content in lung homogenate and significantly reduced the levels of TNF-, IL-1 and IL-6 in lung tissues, and had inhibiting effect on the marked decrease of CD4+ and CD4+/CD8+ [31,32]. Drug Discov. Keywords: Preliminary Study on the Inhibitory Effect of Lianhua Qingwen Capsule on virusMaster Degree. Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. As the Financial Times report showed, these appeared to be serious conflicts of interest as the investments benefited from the PRC and HK governments' rapid approval and then widespread national & international promotion of Lianhua Qingwen and other suspect treatments for purportedly helping COVID-19 sufferers. Lianhua Qingwen capsule and Lianhua Qingwen granules were approved to add "functional indications" to the originally approved indications: "In the conventional treatment of novel. Res. [Lamiaceae; Pogostemonis Botanical drug] (85g), Rheum palmatum L. [Polygonaceae; Rhei Radix et Rhizoma] (51g), Rhodiola crenulata (Hook. [Lamiaceae; 1-Menthol] (7.5g), Glycyrrhiza uralensis Fisch. Jia W., Wang C., Wang Y., Pan G., Jiang M., Li Z., Zhu Y. Qualitative and quantitative analysis of the major constituents in Chinese medical preparation Lianhua-Qingwen capsule by UPLC-DAD-QTOF-MS. Wang C.H., Zhong Y., Zhang Y., Liu J.P., Wang Y.F., Jia W.N., Wang G.C., Li Z., Zhu Y., Gao X.M. [9], During the COVID-19 pandemic, the government of the People's Republic of China (PRC) approved the use of Lianhua Qingwen for mild to moderate COVID-19 cases in January 2020, and promotes the use of the medicine abroad. The group reported significantly lower incidence of adverse reactions (RR = 0.62, 95% CI = 0.460.82) and lower incidence of gastrointestinal system damage in the LHQW group (RR = 0.65, 95% CI = 0.460.92) relative to the control group. Duan Z.P., Jia Z.H., Zhang J., Liu S., Chen Y., Liang L.C., Zhang C.Q., Zhang Z., Sun Y., Zhang S.Q., Wang Y.Y., Wu Y.L. J. Exp. Based on analysis of 40 cases of RCT, the clinical safety of LHQW was comprehensively examined, 163 adverse reactions were reported from 24 studies (Wang et al., 2013). Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. 367 (6485), 14121413. Salvi R., Patankar P. Emerging pharmacotherapies for COVID-19. Our findings support the adverse reactions recorded by Yiling Pharmaceutical, and compare the incidence risk of gastrointestinal system damage and rash with the control group. 81503129, No. Warning 1. Homogeneity of baseline data was reported in most studies. Clin. Subgroup analysis was performed based on adverse reactions and sensitivity analysis implemented to investigate the influence of each study on the overall evaluation by excluding studies in turn. Wang L., Yang Z.H., Zhang H.R., Yu H.X., Yang K., Fu B.H., Yang H.T. [Cruciferae; Isatudus Radix], Dryopteris crassirhizoma Nakai [Polypodiaceae; Dryopteris Crassirhizomatis Rhizoma], Houttuynia cordata Thunb. 2019ZYC-A85), and the Scientific Research Projects of Hospital Pharmacy of Zhejiang Pharmaceutical Association (No. The latest meta-analysis by Fan et al. Moher, D., Liberati, A., Tetzlaff, J., and Altman, D. G.PRISMA Group (2009). "It's the first time in the world that we have enough evidence to prove Lianhua Qingwen capsule is effective and can help . Compared with oseltamivir, LHQW achieved a similar therapeutic effectiveness with reduction of the duration of illness and duration of influenza A virus H1N1 shedding [36]. Niu Q.Q., Chen Y., Liu Y., Mao S.Z., Wang H., Zheng W.K., Zhang J.H. J. Ethnopharmacol. Available at: http://www.plantsoftheworldonline.org (Accessed December 18, 2021). Role of LHQW in the treatment of COVID-19. Here, we performed a meta-analysis of 217 Chinese experimental studies to evaluate the safety of LHQW. The majority of studies lacked sufficient description of allocation concealment and therefore, the project was predominantly evaluated as unclear risk of bias. Although the blinding method was not reported, since some symptom indicators needed measurement with instruments, assessment of symptom indicators was unlikely to be affected by the lack of blinding. With gradual improvement of the adverse drug reaction monitoring system of China, reports of adverse reactions or events have increased. (2020) identified 38 randomized controlled trials (RCTs) comparing LHQW with antivirals or other Chinese medicines for treating influenza and reported a lower risk of adverse reactions in the LHQW group compared to oseltamivir (RR = 0.29, 95%CI = 0.110.80), and ribavirin groups (RR = 0.29, 95%CI = 0.110.80). A Working List of All Plant Species. In the evaluation of security indexes, our meta-analysis revealed that LHQW group having a lower level of adverse reactions compared to the conventional drug group, such as respiratory system damage, skin and its appendage damage, nervous system damage, gastrointestinal system damage and other adverse reactions. Finally, 217 experimental studies on the Chinese population were included for study featuring 1759 cases of adverse reactions following clinical treatment (publication years ranging from 2005 to 2021). However, no consensus has been reached on the security of LHQW to date. doi:10.5582/ddt.2020.03008, PubMed Abstract | CrossRef Full Text | Google Scholar, Cao, B., Zhang, D., and Wang, C. (2020). (Guanghuoxiang), Rheum palmatum L. (Dahuang), Rhodiola rosea Linn. Future related studies will provide accumulated evidence to clarify it. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. The inconsistent use of conventional drugs in individual studies, along with individual differences in drug absorption, may be factors underlying high heterogeneity. [Cruciferae; Isatudus Radix] (255g), Dryopteris crassirhizoma Nakai [Polypodiaceae; Dryopteris Crassirhizomatis Rhizoma] (255g), Houttuynia cordata Thunb. Runfeng L., Yunlong H., Jicheng H., Weiqi P., Qinhai M., Yongxia S., Chufang L., Jin Z., Zhenhua J., Haiming J. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Traditional Chinese medicine, such as Lianhua Qingwen, has achieved some curative effect in many countries, but its effect is not clear. (2020). HHS Vulnerability Disclosure, Help The COVID-19 pneumonia epidemic has spread across the globe poses a significant challenge to public health worldwide. For hand-foot-mouth disease, sample size (p = 0.082), year of publication (p = 0.795), and treatment of the control group (p = 0.701) did not explain the issue of heterogeneity. [19], Although the medicine has been allowed to be sold in Canada since 2012, Health Canada has cautioned against the use of the Chinese traditional medicine to prevent, treat, and cure COVID-19. The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. A recent clinical trial including 36 common cold with wind-heat syndrome patients demonstrated that LHQW (three times daily for four days) treatment could significantly reduce TCM symptom score, with the median time to fever relief of (45) h and the median time to fever clearance of 36h [35]. There are multiple drug trials going on, but there are no specific anti-SARS-CoV-2 drugs or vaccines till now. Mo H.Y., Yang Z.F., Zheng J.P., Mo Z.Y., Li Y.M., Xiao Z.L. ). (2015). However, while the potential clinical efficacy of LHQW has been demonstrated in several studies (Hu et al., 2020; Wu et al., 2020; Xiao et al., 2020; Wang et al., 2021), no consensus has been reached regarding the adverse reactions associated with LHQW therapy to date. Vahl (Lianqiao); Lonicera japonica Thunb. J. Chin. Pharmacol. 'medicine using forsythia suspensa and lonicera japonica to clear illness',[1] LHQW) is a traditional Chinese medicine (TCM) formulation used for the treatment of influenza. Zhu S.Y., Li X.Y., Wei Y.L., Yang P.Y., Qin E.D. Common side effects are heart palpitations, nausea, and vomiting. The current meta-analysis was performed to evaluate the safety profile of LHQW in relation to conventional drugs (PROSPERO CRD-42020224180). Tradit. (2021). Patients with severe cases will develop acute respiratory distress syndrome and septic shock, and eventually develop multi-organ failure and death [5]. In recent years, LHQW has played a significant role in the prevention and control of viral public health events (Yao et al., 2020), and is widely accepted as a representative antiviral Chinese medicine in China. [4] Its formulation includes 13 herbs which are said to have been used for medical purposes as early as the Han dynasty. showed that the usual treatment in combination with LHQW capsules (4 capsules thrice daily for 14 days) had significantly higher recovery rate, and shorter median time to symptom recovery, as compared with control group [43]. Royal Botanic Gardens, Kew (2021). As adverse reactions in COVID-19 pneumonia and chronic obstructive pulmonary disease treatment were only reported for a limited number of studies, no sensitivity analysis for these diseases was conducted. Meanwhile, the median effective concentrations (EC50) in above-mentioned effects were 0.042, 0.031, 0.051 and 0.050mg/mL, respectively, while the prevention effect on virus adsorption was the strongest [25]. Med. The different incidence of these adverse reactions may be related to the metabolic level, which varies greatly among the different age groups. We would like to express our appreciation to all authors of eligible studies which were included in the current meta-analysis. TABLE 2. Subgroup, sensitivity and meta-regression analyses were conducted to explore the possible sources of heterogeneity across eligible studies. (2015). Pharmacol. Twenty-three studies on other diseases were included, with 12 reporting adverse reactions. Therefore, people have also observed that Lianhua Qingwen capsule (granule) inhibits the over-expression of human common coronavirus (HcV-229E), novel coronavirus (COVID-19) infected cells and. Please be informed that only the Lianhua . The recent meta analysis reported 22 studies with a total of 2,007 patients, showing that the adjuvant therapy of LHQW with western medicine could improve the clinical efficiency and C-reactive protein index, shorten the time of antifebrile, cough time, rhondros duration and imaging time, as well as speed up the recovery of pneumonia patients [39]. Effect of Lianhua Qingwen capsule on immunity of mice infected with flu virus. Keywords: Lianhua Qingwen capsule; Meta-analysis; influenza; systematic review. There was no statistically significant difference in the incidence of adverse reactions during treatment of chronic obstructive pulmonary disease between the LHQW group and the conventional drug group (RR = 1.27, 95% CI = 0.513.17, p = 0.608). Clinical Practice Guideline on Treating Influenza in Adult Patients with Chinese Patent Medicines. 161, 105126. doi:10.1016/j.phrs.2020.105126, Yang, C., Wang, Y., He, J., Yan, W., Jiang, H., Chen, Q., et al. doi:10.1016/0197-2456(86)90046-2, Duval, S., and Tweedie, R. (2000). Advances in Pharmacology and Clinical Research of Lianhua Qingwen Capsules. Two studies reported psychiatric disorders as the adverse reaction. *Correspondence: Guoliang Zhang, [email protected], These authors have contributed equally to this work, https://doi.org/10.3389/fphar.2022.764774, World Health Organization Adverse Drug Reaction Terminology (2009), https://www.frontiersin.org/articles/10.3389/fphar.2022.764774/full#supplementary-material, http://m.news.cctv.com/2020/03/17/ARTIEYQ2aws8fPYWQxjnynzo200317.shtml?from=singlemessage, https://mpns.science.kew.org/mpns-portal/, https://chemrxiv.org/engage/chemrxiv/article-details/60c74908ee301c485bc799cf, http://www.yiling.cn/contents/75/132.html. Available at: https://mpns.science.kew.org/mpns-portal/(Accessed December 19, 2021). Cui L.F., Xu H.R., Li F.Z., Wang C.X. 2015, 731765. doi:10.1155/2015/731765, Jin, L., Xu, Y., and Yuan, H. (2020). It was found that the total effective rate of LHQW granules combined with abidor treatment (LHQW group) was significantly higher than that of abidor group (80.95 % vs 64.86 %), while the rate of severe illness was markedly lower (14.29 % vs 23.65 %) [44]. Some composition of LHQW can cause damage to the stomach and intestines, supporting the possibility of injurious effects on the gastrointestinal system: for thia suspensa (Thunb.) Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. Now, there are no study results posted on ClinicalTrials.gov for this study yet. Traditional Chinese medicine formulation used for the treatment of influenza, Uses and controversies of Lianhua Qingwen in relation to COVID-19, by region, "How traditional Chinese medicine TCM is used to treat Covid-19", "The mechanisms and clinical application of Traditional Chinese Medicine Lianhua-Qingwen capsule", "Clinical applications and pharmacological research progress of Lianhua Qingwen capsules/granules", "Traditional Chinese cures battle for acceptance in COVID-19 fight", "Chinese traditional medicine for Covid-19 becomes money tree", "Efficacy of Lianhua Qingwen Compared with Conventional Drugs in the Treatment of Common Pneumonia and COVID-19 Pneumonia: A Meta-Analysis", "Doctors warn against claims that Beijing-touted health supplement distributed in Canada treats COVID-19", "The Adverse Reactions of Lianhua Qingwen Capsule/Granule Compared With Conventional Drug in Clinical Application: A Meta-Analysis", "Beijing pushes traditional Chinese medicine as coronavirus treatment", "China Covid-19 tsar pushed treatments without revealing business ties", "Efficacy and Safety of Lianhuaqingwen Capsules, a repurposed Chinese Herb, in Patients with Coronavirus disease 2019: A multicenter, prospective, randomized controlled trial", "Prominent Chinese scientist failed to disclose company ties in COVID-19 clinical trial paper", "DOH and FDA Clarify Claims on the Approval of Potential COVID-19 Treatments and Calls for Resignation of the SoH", "Lianhua Qingwen, the FDA-approved traditional Chinese med, only treats symptoms, not COVID", "HSA Advisory on Lianhua Qingwen Products for Prevention or Treatment of COVID-19", "Fraudulent Coronavirus Disease 2019 (COVID-19) Products", "Chinese medicine Lianhua Qingwen makes its way into community for COVID-19 treatment despite Australian ban", https://en.wikipedia.org/w/index.php?title=Lianhua_Qingwen&oldid=1143380058, Short description is different from Wikidata, Articles needing expert attention from January 2023, Medicine articles needing expert attention, Articles containing simplified Chinese-language text, Articles containing traditional Chinese-language text, Articles with unsourced statements from August 2022, Creative Commons Attribution-ShareAlike License 3.0, Treatment against various respiratory diseases including, This page was last edited on 7 March 2023, at 11:01. cathy sparks bio, connors health score huntsville, al,

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