Objective To compare the effects of dexmedetomidine and midazolam on intraoperative blood pressure and postoperative 90-day outcome of endovascular treatment(EVT)in patients with acute anterior circulation large vessel occlusive stroke.Methods Retrospective consecutive patients with acute anterior circulation large vessel occlusion stroke who received EVT within 24 hours of onset,admitted to the Department of Neurology at the Second People's Hospital of Hefei from January 2024 to February 2025 were included.Patients were divided into the dexmedetomidine group and the midazolam group based on the choice of sedative in EVT.Baseline and clinical data were collected from patients,including sex,age,medical history(hypertension,diabetes,atrial fibrillation,stroke history),smoking history,blood pressure at admission(systolic,diastolic,mean arterial pressure),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,and site of vascular occlusion(internal carotid artery,M1 segment of the middle cerebral artery).Procedure related parameters,including intravenous thrombolysis before EVT,intraoperative use of tirofiban,modified thrombolysis in cerebral infarction(mTICI)grade,thrombectomy techniques(stent-retriever thrombectomy,aspiration thrombectomy,combined stent-retriever and aspiration thrombectomy,and other salvage measures),number of thrombectomy,time from onset to revascularization,time from puncture to revascularization,blood pressure during EVT(minimum systolic,minimum diastolic,and minimum mean arterial pressure),and blood pressure at the end of EVT(systolic,diastolic,and mean arterial pressure).The primary outcome was good prognosis at 90 days after EVT(modified Rankin scale score of 0-2 at 90 days),while secondary outcome was＞20％decrease in mean arterial pressure during EVT,early neurological improvement(ENI;a decrease on NIHSS score no less than 8 or a reduction of NIHSS score to 0-1 at 24 hours after EVT),and early neurological deterioration(END;an increase of more than 2 points on the NIHSS at 24 hours after procedure).Safety outcomes included any intracranial hemorrhage within 48 hours after EVT,symptomatic intracranial hemorrhage within 48 hours after EVT(sICH;intracranial hemorrhage confirmed by head CT leading to neurological deterioration,with an increase in NIHSS score of at least 4 points,or the presence of potentially fatal intracranial hemorrhage on head CT),pneumonia within 2 weeks after EVT,and the 90-day mortality after EVT.The baseline and clinical data,EVT conditions,primary outcome,secondary outcome,and safety indicators were compared between the two groups.Univariate Logistic regression analysis was used to screen the variables associated with a decrease in mean arterial pressure＞20％during EVT in patients with acute anterior circulation large vessel occlusive stroke.Variables with P＜0.15 and those considered potentially influential based on clinical experience were included in multivariate Logistic regression analysis to identify predictors of a＞20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Results A total of 93 patients with acute anterior circulation large vessel occlusive stroke who underwent EVT were included,comprising 51 males and 42 females,aged 34 to 99 years,with an average of(71±13)years old.Among them,63 patients were in the dexmedetomidine group,and 30 patients were in the midazolam group.33 patients showed＞20％decreases in mean arterial pressure during EVT,while 60 patients had ≤20％decreases.(1)Compare with the midazolam group,the proportion of female patients in the dexmedetomidine group was lower(36.5％[23/63]vs.63.3％[19/30],P=0.015),and the age was younger([69±13]years vs.[77±13]years,P=0.005).There were no statistically significant differences in other baseline and clinical data(all P＞0.05).(2)In comparison with the midazolam group,the dexmedetomidine group had a higher proportion of patients with more thrombectomy procedures(1.00[1.00,2.00]times vs.1.00[1.00,1.25]times,P=0.011),END(27.0％[17/63]vs.6.7％[2/30],P=0.023),sICH within 48 hours(19.0％[12/63]vs.3.3％[1/30],P=0.041),and a decrease in mean arterial pressure＞20％during EVT(42.9％[27/63]vs.20.0％[6/30],P=0.031).There were no statistically significant differences in the remaining EVT conditions,primary outcome,secondary outcome,and safety indicators(all P＞0.05).(3)The results of univariate Logistic regression analysis showed that diastolic blood pressure at admission(P=0.002),mean arterial pressure at admission(P=0.009),and dexmedetomidine sedation(P=0.036)were the influencing factors of a decrease＞20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusion stroke.(4)The results of multivariate Logistic regression analysis showed that dexmedetomidine sedation(OR,3.271,95％CI 1.057-10.126,P=0.040)and higher diastolic blood pressure on admission(OR,1.105,95％CI 1.006-1.213,P=0.037)were independent predictors of a decrease over 20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Conclusions Dexmedetomidine is an independent predictor of an over 20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke,but there is no statistically significant differences in the rate of good neurological function at 90 days and 90-day mortality postoperatively between the two groups.Further prospective randomized controlled studies are needed.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To compare the effects of dexmedetomidine and midazolam on intraoperative blood pressure and postoperative 90-day outcome of endovascular treatment(EVT)in patients with acute anterior circulation large vessel occlusive stroke.Methods Retrospective consecutive patients with acute anterior circulation large vessel occlusion stroke who received EVT within 24 hours of onset,admitted to the Department of Neurology at the Second People's Hospital of Hefei from January 2024 to February 2025 were included.Patients were divided into the dexmedetomidine group and the midazolam group based on the choice of sedative in EVT.Baseline and clinical data were collected from patients,including sex,age,medical history(hypertension,diabetes,atrial fibrillation,stroke history),smoking history,blood pressure at admission(systolic,diastolic,mean arterial pressure),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,and site of vascular occlusion(internal carotid artery,M1 segment of the middle cerebral artery).Procedure related parameters,including intravenous thrombolysis before EVT,intraoperative use of tirofiban,modified thrombolysis in cerebral infarction(mTICI)grade,thrombectomy techniques(stent-retriever thrombectomy,aspiration thrombectomy,combined stent-retriever and aspiration thrombectomy,and other salvage measures),number of thrombectomy,time from onset to revascularization,time from puncture to revascularization,blood pressure during EVT(minimum systolic,minimum diastolic,and minimum mean arterial pressure),and blood pressure at the end of EVT(systolic,diastolic,and mean arterial pressure).The primary outcome was good prognosis at 90 days after EVT(modified Rankin scale score of 0-2 at 90 days),while secondary outcome was＞20％decrease in mean arterial pressure during EVT,early neurological improvement(ENI;a decrease on NIHSS score no less than 8 or a reduction of NIHSS score to 0-1 at 24 hours after EVT),and early neurological deterioration(END;an increase of more than 2 points on the NIHSS at 24 hours after procedure).Safety outcomes included any intracranial hemorrhage within 48 hours after EVT,symptomatic intracranial hemorrhage within 48 hours after EVT(sICH;intracranial hemorrhage confirmed by head CT leading to neurological deterioration,with an increase in NIHSS score of at least 4 points,or the presence of potentially fatal intracranial hemorrhage on head CT),pneumonia within 2 weeks after EVT,and the 90-day mortality after EVT.The baseline and clinical data,EVT conditions,primary outcome,secondary outcome,and safety indicators were compared between the two groups.Univariate Logistic regression analysis was used to screen the variables associated with a decrease in mean arterial pressure＞20％during EVT in patients with acute anterior circulation large vessel occlusive stroke.Variables with P＜0.15 and those considered potentially influential based on clinical experience were included in multivariate Logistic regression analysis to identify predictors of a＞20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Results A total of 93 patients with acute anterior circulation large vessel occlusive stroke who underwent EVT were included,comprising 51 males and 42 females,aged 34 to 99 years,with an average of(71±13)years old.Among them,63 patients were in the dexmedetomidine group,and 30 patients were in the midazolam group.33 patients showed＞20％decreases in mean arterial pressure during EVT,while 60 patients had ≤20％decreases.(1)Compare with the midazolam group,the proportion of female patients in the dexmedetomidine group was lower(36.5％[23/63]vs.63.3％[19/30],P=0.015),and the age was younger([69±13]years vs.[77±13]years,P=0.005).There were no statistically significant differences in other baseline and clinical data(all P＞0.05).(2)In comparison with the midazolam group,the dexmedetomidine group had a higher proportion of patients with more thrombectomy procedures(1.00[1.00,2.00]times vs.1.00[1.00,1.25]times,P=0.011),END(27.0％[17/63]vs.6.7％[2/30],P=0.023),sICH within 48 hours(19.0％[12/63]vs.3.3％[1/30],P=0.041),and a decrease in mean arterial pressure＞20％during EVT(42.9％[27/63]vs.20.0％[6/30],P=0.031).There were no statistically significant differences in the remaining EVT conditions,primary outcome,secondary outcome,and safety indicators(all P＞0.05).(3)The results of univariate Logistic regression analysis showed that diastolic blood pressure at admission(P=0.002),mean arterial pressure at admission(P=0.009),and dexmedetomidine sedation(P=0.036)were the influencing factors of a decrease＞20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusion stroke.(4)The results of multivariate Logistic regression analysis showed that dexmedetomidine sedation(OR,3.271,95％CI 1.057-10.126,P=0.040)and higher diastolic blood pressure on admission(OR,1.105,95％CI 1.006-1.213,P=0.037)were independent predictors of a decrease over 20％in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke.Conclusions Dexmedetomidine is an independent predictor of an over 20％decrease in mean arterial pressure during EVT in patients with acute anterior circulation large vessel occlusive stroke,but there is no statistically significant differences in the rate of good neurological function at 90 days and 90-day mortality postoperatively between the two groups.Further prospective randomized controlled studies are needed.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.

Objective To investigate the correlation between the hemoglobin glycation index(HGI)and the severity of intraplaque neovascularization(IPN)in patients with mild-to-moderate carotid artery stenosis.Methods This study retrospectively and consecutively enrolled patients with mild-to-moderate carotid artery stenosis(＜70%narrowing)hospitalized in the Department of Neurology at the Hefei Second People's Hospital between June,2020 and June,2024.Demographic data(age,gender),personal history(smoking,drinking),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia),body mass index,and laboratory indicators from fasting venous blood collected on the second morning of hospital admission(neutrophils,lymphocytes,neutrophil-to-lymphocyte ratio,platelet count,total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol(LDL-C),homocysteine,blood glucose,and glycated hemoglobin[HbA1c])were collected and compared.A univariate linear regression analysis was performed to assess the relationship between fasting blood glucose and HbA1c levels measured on the second day after admission,yielding the prediction formula:predicted HbA1c(%)=0.571×fasting blood glucose(mmol/L)+3.125.Subsequently,HGI was calculated through:HGI=actual HbA1c-predicted HbA1c.Carotid ultrasound was used to measure patients'carotid intima-media thickness,and,plaque location,thickness(maximum plaque diameter),length,echogenicity,and resistance index.For patients with multiple plaques,the thickest plaque was selected as the target plaque.Using the AngioPLUS mode of carotid ultrasound,dynamically observe for presence of IPN at the filling defect of the carotid artery plaque.The IPN condition of the target plaque was then assessed,including the number,location,morphology(e.g.,punctate,short linear,etc.),and spectral Doppler characteristics of the new blood vessels.The IPN signals were counted and scored according to the following criteria:absence of high-echogenicity blood flow signals in the target carotid artery plaque indicating no neovascularization,was scored as 0 point;the presence of fewer than 4 punctate or short linear hyperechoic blood flow signals within the target plaque was scored as 1 point;the presence of diffusely distributed(≥4)short linear or strip-like hyperechoic blood flow signals within the plaque was scored as 2 points.A higher IPN score indicates a more severe degree of IPN.Patients with an IPN score of 0-1 were categorized as the low IPN score group,while those with an IPN score of 2 were classified as the high IPN score group.Indicators with statistically significant differences between the two groups in the univariate analysis and exhibited no multicollinearity were included in the multivariate binary Logistic regression model to analyze the relationship between HGI and the severity of carotid IPN.Results A total of 387 patients(222 males and 165 females,with a mean age of[70±10]years)with mild-to-moderate carotid artery stenosis were included in this study.Among the 387 patients enrolled,97 were in the low IPN score group,while 290 were in the high IPN score group.(1)The high IPN score group exhibited significantly higher average age([71±10]years vs.[67±10]years),higher prevalence of hypertension(79.7%[231/290]vs.67.0%[65/97]),higher prevalence of diabetes(37.6%[109/290]vs.14.4%[14/97]),greater plaque thickness(2.40[2.00,3.10]mm vs.2.30[1.80,2.70]mm),higher HbA1c levels(6.25%[5.70%,7.20%]vs.5.80%[5.50%,6.40%]),and higher HGI values(-0.05%[-0.39%,0.46%]vs.-0.29%[-0.56%,-0.10%])in comparison to the low IPN score group(all P＜0.05).Additionally,the high IPN score group had significantly lower lymphocyte ratios([27.75±9.19]%vs.[30.17±9.04]%)and lower LDL-C levels([2.19±0.81]mmol/L vs.[2.43±0.91]mmol/L;both P＜0.05).(2)The results of multivariate Logistic regression analysis indicated that age(OR,1.031,95%CI 1.004-1.060,P=0.027),HGI(OR,1.782,95%CI 1.066-2.979,P=0.028),and plaque thickness(OR,1.750,95%CI 1.229-2.490,P=0.002)were independent influencing factors associated with the severity of IPN in the mild-to-moderate carotid artery stenosis.Conclusions High HGI may serve as an independent risk factor for the severe IPN in patients with mild-to-moderate carotid artery stenosis.However,the findings of this study require further validation through multi-center,large-scale,prospective clinical trials.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

Basket trial, as an innovative clinical trial design concept, marks the transformation of medical research from the traditional large-scale and single-disease treatment to the precise and individualized treatment. By gradually incorporating the Bayesian method during development, the trial design becomes more scientific and reasonable and increases its efficiency. The fundamental principle of the Bayesian method is the utilization of prior knowledge in conjunction with new observational data to dynamically update the posterior probability. This flexibility enhances the basket trial's capacity to effectively adapt to variations during the research process. Consequently, it enables researchers to dynamically adjust research strategies based on accumulated data and improve the predictive accuracy regarding treatment responses. In addition, the design concept of the basket trial aligns with the traditional Chinese medicine(TCM) principle of "homotherapy for heteropathy". The principle of "homotherapy for heteropathy" emphasizes that under certain conditions, different diseases may have the same treatment. Similarly, basket trials allow using a uniform trial design across multiple diseases, offering enhanced operational and significant practical value in the realm of TCM, particularly within the context of syndrome-based disease research. By introducing basket trials, the design of TCM clinical studies will be more scientific and yield higher-quality evidence. This study systematically categorized various Bayesian methods and models utilized in basket trials, evaluated their strengths and weaknesses, and identified their appropriate application contexts, so as to offer a practical guide for designing basket trials in the realm of TCM.
Bayes Theorem ; Humans ; Medicine, Chinese Traditional/methods* ; Research Design ; Clinical Trials as Topic/methods* ; Drugs, Chinese Herbal/therapeutic use*