ObjectiveTo analyze the volatile components in raw Coptidis Rhizoma， Euodiae Fructus juice-processed Coptidis Rhizoma （Yuhuanglian）， and the processing adjuvant Euodiae Fructus juice， identify marker volatile components in the processed product， and elucidate the material basis changes during the processing with Euodiae Fructus juice. MethodsHeadspace solid-phase microextraction coupled with gas chromatography-quadrupole-time-of-flight mass spectrometry （HS-SPME-GC-Q-TOF-MS） was employed to analyze the volatile components in raw Coptidis Rhizoma， Yuhuanglian， and Euodiae Fructus juice. Chemometric analysis was performed to compare volatile components among samples and screen the marker components. Finally， the relative odor activity value （ROAV） was calculated to investigate odor characteristics. ResultsA total of 127 components were detected， with 27， 75， 84 volatile components identified in Euodiae Fructus juice， raw Coptidis Rhizoma， and Yuhuanglian， respectively. Processing with Euodiae Fructus juice significantly increased the number and content of volatile components. Chemometric analysis revealed significant changes in volatile components among the three sample types， allowing clear discrimination. After processing， 39 components such as methyl octanoate and allyl propionate were introduced， while 34 components including furfural and hexanoic acid increased in content， and 11 components including butyric acid and octanal decreased. Additionally， eight components， including zingiberene， 6-methyl-6-hepten-2-one， and 5-methyl-2-hexanone， were screened as marker components of Yuhuanglian. Moreover， processing enhanced the ROAV values of 2，5-dimethylpyrazine （roasted， nutty， coffee-like aroma）， 3-ethylphenol， and guaiacol （smoky， woody aroma）. Additionally， it incorporated 1-hepten-3-one from Euodiae Fructus juice and the newly generated 1-hexen-3-one， contributing mushroom and cucumber-like odors. The sensory profile of Yuhuanglian integrated nutty， roasted， smoky， and woody notes with the citrus and fruity aroma originally contributed by octanal. ConclusionThe processing with Euodiae Fructus juice introduced components from adjuvant， significantly altering the volatile component profile and enhancing the sensory odor characteristics of Yuhuanglian. This study provides a valuable reference for exploring the material basis of volatile components and establishing processing specifications for Yuhuanglian.

ObjectiveTo analyze the volatile components in raw Coptidis Rhizoma， Euodiae Fructus juice-processed Coptidis Rhizoma （Yuhuanglian）， and the processing adjuvant Euodiae Fructus juice， identify marker volatile components in the processed product， and elucidate the material basis changes during the processing with Euodiae Fructus juice. MethodsHeadspace solid-phase microextraction coupled with gas chromatography-quadrupole-time-of-flight mass spectrometry （HS-SPME-GC-Q-TOF-MS） was employed to analyze the volatile components in raw Coptidis Rhizoma， Yuhuanglian， and Euodiae Fructus juice. Chemometric analysis was performed to compare volatile components among samples and screen the marker components. Finally， the relative odor activity value （ROAV） was calculated to investigate odor characteristics. ResultsA total of 127 components were detected， with 27， 75， 84 volatile components identified in Euodiae Fructus juice， raw Coptidis Rhizoma， and Yuhuanglian， respectively. Processing with Euodiae Fructus juice significantly increased the number and content of volatile components. Chemometric analysis revealed significant changes in volatile components among the three sample types， allowing clear discrimination. After processing， 39 components such as methyl octanoate and allyl propionate were introduced， while 34 components including furfural and hexanoic acid increased in content， and 11 components including butyric acid and octanal decreased. Additionally， eight components， including zingiberene， 6-methyl-6-hepten-2-one， and 5-methyl-2-hexanone， were screened as marker components of Yuhuanglian. Moreover， processing enhanced the ROAV values of 2，5-dimethylpyrazine （roasted， nutty， coffee-like aroma）， 3-ethylphenol， and guaiacol （smoky， woody aroma）. Additionally， it incorporated 1-hepten-3-one from Euodiae Fructus juice and the newly generated 1-hexen-3-one， contributing mushroom and cucumber-like odors. The sensory profile of Yuhuanglian integrated nutty， roasted， smoky， and woody notes with the citrus and fruity aroma originally contributed by octanal. ConclusionThe processing with Euodiae Fructus juice introduced components from adjuvant， significantly altering the volatile component profile and enhancing the sensory odor characteristics of Yuhuanglian. This study provides a valuable reference for exploring the material basis of volatile components and establishing processing specifications for Yuhuanglian.

Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature， and ginger is used to restrict the bitter cold of Coptidis Rhizoma， which can be traced back to Bojifang， and it is suitable for stagnation of damp-heat in middle-jiao， cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids， phenylpropanoids and flavonoids of Coptidis Rhizoma， and also introduces gingerol components such as 6-gingerol in ginger， which has pharmacological activities such as anti-inflammatory， antibacterial， anti-tumor， and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian， but the specific process parameters and quality standards are incomplete， which limits the production and clinical application of this processed product. By summarizing the processing history， process research， quality evaluation， pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years， there are differences in the processing methods and standards in various provinces and cities， which are mainly reflected in the preparation method， dosage， processing process and quantitative standards of ginger juice. In addition， there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger， as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards， and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Objective To investigate the key factors influencing the implementation of long-acting injection-promoting policies and propose effective improving paths.Methods Qualitative interviews were carried out for stakeholders involved in the promotion of long-acting injections,based on the consolidated framework for implementation research.Additionally,countermeasures for identified barriers were proposed based on expert recommendations for implementation changes.Results A total of 46 health administrators,healthcare workers,and patients in Beijing were interviewed.The study identified several barriers in the strength and quality of evidence,adaptability,relative advantage,complexity and cost,patient needs and resources,external collaboration,external policies and incentives,organizational structural characteristics,and self-efficacy.Conclusions From the perspectives and experiences of stakeholders,the promotion of long-acting injections has shown initial success but still faces multiple obstacles.It is recommended that efforts should be made to coordinate and adapt policies,improve and incentivize relative organizations,and continuously strengthen the advocacy and education for individuals.
Humans ; Beijing ; Delayed-Action Preparations ; Health Personnel ; Health Policy ; Injections

Objective To gain insights into the care service preferences and willingness of patients with severe mental disorders in Beijing,analyze the main factors affecting their participation in care services,and provide data support and decision-making reference for the optimal design of care services for patients with severe mental disorders and the improvement of relevant policies.Methods In July 2022,a questionnaire survey was conducted for a part of Beijing community patients with severe mental disorders selected by multi-stage stratified sampling,including the basic personal information and the preferences of discrete choice experiment.A mixed Logit model was used to perform regression analysis on the care service preferences,and the trade off between general and monetary attributes was quantified by willingness to pay(WTP).Results A total of 242 questionnaires were distributed,and 181 valid questionnaires were collected,with a response rate of 74.79%.The regression coefficients for the four attributes-service type,service content,service frequency,and service cost-all showed statistical significance(all P<0.05).Patients' most preferred attribute level was a service frequency covering about 90% of the time per month/year( β=1.059),while the least preferred was full-time residential care( β=-1.025).Increasing the service frequency from 30% to 90% corresponded to a WTP of 492.5 yuan,while changing the service type from home-based care to full-time residential care resulted in a WTP of -476.6 yuan.Moreover,there were differences in care service preferences and WTP among patient groups with different characteristics(all P<0.05).Conclusions Service type,service content,service frequency,and service cost all significantly affect the care service preferences of patients with severe mental disorders.There is heterogeneity in care service preferences among patient groups with different characteristics.
Humans ; Mental Disorders/therapy* ; Patient Preference ; Beijing ; Surveys and Questionnaires ; Male ; Female ; Choice Behavior ; Adult ; Middle Aged

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.