As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

As an exclusive Miao medicine of Honwing Pharma （Guizhou） Co. Ltd.， Yifei Zhike capsules are both a prescription drug and an over-the-counter （OTC） drug. Its main ingredients include Ranunculus ternatus and Panax notoginseng. With the effects of nourishing Yin and moistening the lungs， as well as relieving cough and reducing phlegm， Yifei Zhike capsules are often used in the treatment of acute and chronic bronchitis， pulmonary tuberculosis， and other diseases. However， there is insufficient understanding of their efficacy， suitable syndromes， and safety in clinical practice， with a lack of relevant expert consensus on clinical application. To standardize their clinical application， 30 experts from the fields of respiratory medicine， pharmacy， and evidence-based medicine were invited to develop an Expert Consensus on the Clinical Application of Yifei Zhike Capsules （Consensus for short） through evidence-based medicine methods. The Consensus clarified the syndrome characteristics， disease stages， dosages， treatment courses， combined medication， and other norms in the treatment of acute/chronic bronchitis and pulmonary tuberculosis and could be applicable to clinical physicians and pharmacists in medical and health institutions at all levels. In disease diagnosis， it provided diagnostic criteria for traditional Chinese medicine and Western medicine and clarified that the suitable traditional Chinese medicine syndrome was the syndrome of Qi-Yin deficiency with intermingled phlegm-blood stasis. Clinical studies have confirmed that Yifei Zhike capsules combined with standard anti-tuberculosis therapy can effectively improve the symptoms of pulmonary tuberculosis patients， increase the sputum smear conversion rate， and promote the absorption of lesions. When treating acute cough caused by respiratory tract infections， Yifei Zhike capsules can increase the markedly effective rate and the seven-day disappearance rate of cough symptoms. Meanwhile， recommendations for specific usage， dosages， and treatment courses were given for different diseases， and it was pointed out that long-term medication required key monitoring of adverse reactions. In safety， the adverse reactions of Yifei Zhike capsules involved multiple aspects such as the digestive system and allergic reactions， and pregnant women and women during menstruation were prohibited from using it. In addition， modern research has shown that Yifei Zhike capsules have an adjuvant therapeutic effect on tuberculous pleurisy and may be effective for inflammatory and benign pulmonary nodules. However， further research should be conducted on the toxicological safety of long-term medication. The formulation of the Consensus provides a scientific basis for the rational clinical application of Yifei Zhike capsules， which helps to improve clinical efficacy and reduce medication risks.

Periodontal homeostasis is regulated by the complex interplay between the gingival epithelial barrier, the extracellular matrix of soft tissues, the bone coupling system, and immune responses within the periodontal region. Gingival epithelial cells are primarily composed of keratinocytes and a small proportion of non-keratinocytes, and they are integral to the formation of the gingival epithelial barrier. This epithelial barrier plays a fundamental role in defending against pathogens, exogenous substances, and mechanical stress. This study aims to explore the intrinsic connections between gingival epithelial cells and periodontal homeostasis. Research has shown that gingival epithelial cells participate in maintaining periodontal homeostasis through multiple pathways: ① gingival epithelial cells respond to the inflammatory environment by undergoing proliferation, migration, epithelial-mesenchymal transition, and forming apoptosis-mediated neutrophil extracellular traps; ② when gingival inflammation damages the epithelial barrier, lipopolysaccharides cannot be easily removed, and gingival epithelial cells play a defensive role by activating innate immune responses; ③ the interactions of gingival epithelial cells with oral microbiota and immune cells are essential for maintaining periodontal homeostasis. Thus, gingival epithelial cells are closely associated with periodontal homeostasis. However, the crucial role and mechanisms of gingival epithelial cells in the maintenance of periodontal homeostasis are not clear, which provides novel insights for the research of periodontal homeostatic medicine.

The compilation instructions for the Expert Consensus on Clinical Application of Yifei Zhike Capsules systematically expound the development background， methodological framework， and core achievements of this consensus. In view of the problems existing in the clinical application of Yifei Zhike Capsules， such as insufficient efficacy evidence and lack of standardized syndrome differentiation， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences took the lead and collaborated with 21 tertiary grade-A hospitals and research institutions across China to form a multidisciplinary expert group （comprising 30 experts in clinical medicine， pharmacy， and methodology）. The compilation work was carried out in strict accordance with the World Health Organization （WHO） guidelines， the GB/T 1.1-2020 standard， and the writing specifications for the explanatory notes of expert consensus on clinical application of Chinese patent medicines. Through systematic literature retrieval （including 32 studies， with 24 clinical studies）， Grading of Recommendations Assessment， Development and Evaluations （GRADE）-based evidence grading， and multiple rounds of discussions using the nominal group method （25 experts voted to determine 17 clinical questions）， 5 evidence-based recommendations and 11 expert consensus suggestions were formed. It is clarified that this medicine （Yifei Zhike Capsules） is applicable to the treatment of expectoration/hemoptysis in acute and chronic bronchitis and the adjuvant treatment of pulmonary tuberculosis. It is recommended that it can be used alone or in combination with anti-tuberculosis drugs. The safety evaluation shows that this medicine mainly induces the following adverse reactions： mild gastrointestinal reactions （such as nausea and abdominal pain） and rashes. The contraindicated populations include pregnant women and women during menstruation. The compilation process of the consensus underwent three rounds of expert letter reviews， two rounds of peer reviews， and quality control assessments to ensure methodological rigor and clinical applicability. In addition， through policy alignment， academic promotion， and a dynamic revision mechanism， the standardization of clinical application was promoted， providing a demonstration for the evidence-based transformation of characteristic therapies of Miao medicine.

The field of post-marketing benefit-risk assessment for traditional Chinese medicine（TCM） is still in its nascent stage， lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM， and explored the critical techniques and specific implementation steps involved in the assessment process. Initially， appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently， key technologies were outlined， including the establishment of a benefit-risk indicator system， the assignment of indicator weights， and the definition of criteria attributes. Furthermore， the implementation steps were elaborated， which involved defining decision-making issues， data collection， evaluation methodologies， variability factors， and sensitivity analysis. Finally， a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.

Objective:To observe the effects of different repair methods in the defects after Mohs surgical excision of malignant nasal tumors. Methods:Twenty-two cases of external nasal malignant tumor surgery from January 2021 to May 2024 were selected as the research. The tumors were resected using Mohs surgical technique, and the defects were repaired using forehead axial flap, bipedicle flap, nasolabial flap, free full-thickness skin graft from the groin, forehead axial flap, facial kite flap, and composite flap of earlobe cartilage and perichond. The postoperative flap survival, external nasal morphology, and tumor recurrence were observed. Results:Among the 22 cases, there were 1 case of Kaposis sarcoma（KS）, 2 cases of squ cell carcinoma, and 19 cases of basal cell carcinoma. Tumors were located at the nasal root in 3 cases, the nasal dorsum in5 cases, the nasal tip in 2 cases, the ala in 8 cases, both the ala and the nasal dorsum in 2 cases, nasal columella, the nasal tip, and the ala in 1 case, the nasal tip, the nasal dorsum, the ala, and paranasal area in 1 case. The size of the defects ranged from 1.2 cm×1.4 cm to 3.7 cm×4.8 cm. Three cases were repaired with forehead axial flaps, four cases with bilobed flaps, thirteen cases with nasolabial groove flaps, one case with free full-thickness skin grafts from the inguinal region, and one case with a combination of forehead axial flaps and facial kite flaps plus a composite of earlobe cartilage and perichondrium. All flaps survived well after surgery. Patients were followed up for 6 months to 3 years after surgery, during which no tumor recurrence was observed, and most patients were satisfied with appearance of their nose. Conclusion:Mohs surgery is used to excise the malignant tumor of the external nose, and satisfactory surgical results can be obtained by using different repair methods based the location and size of the postoperative defect.
Humans ; Mohs Surgery/methods* ; Nose Neoplasms/surgery* ; Surgical Flaps ; Skin Transplantation ; Male ; Carcinoma, Basal Cell/surgery* ; Skin Neoplasms/surgery* ; Female ; Middle Aged ; Plastic Surgery Procedures/methods* ; Nose/surgery* ; Aged ; Adult ; Carcinoma, Squamous Cell/surgery*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To develop a size exclusion-high-performance liquid chromatography(SEC-HPLC) method for the simultaneous determination of free proteins and residual 4-dimethylaminopyridine(DMAP) in the bulk solution of pneumococcal polysaccharide-protein conjugate, and to verify and preliminarily apply the method.Methods By studying the characteristic ultraviolet absorption peak of DMAP and optimizing the separation method of chromatographic column, the SEC-HPLC method was established to realize the retention and separation of free proteins and DMAP on the same chromatographic column and quantify them. The method was verified for specificity(system suitability), limit of quantification(LOQ), accuracy, precision, linearity and range, and robustness, and was used to detect the free proteins and DMAP residues in the test sample.Results The chromatographic conditions were determined as follows: TSKgel G5000 PWXL analytical column was used as the column(7. 8 mm × 300 mm, 10 ??m), the column temperature was set at 35 ℃, the mobile phase was0. 85% sodium chloride solution, the pH was(6. 2 ± 0. 2), the flow rate was 0. 5 mL/min, and the detection wavelength was280 nm. The resolution of free protein peaks of diphtheria toxoid(DT) or tetanus toxoid(TT) and DMAP peak from adjacent peaks was greater than 1. 5. The LOQs of TT, DT and DMAP were 0. 50, 1. 20, and 0. 02 ??g/mL, respectively. The spiked recovery rates of TT, DT and DMAP were 98. 11%-104. 60%, 95. 43%-103. 26% and 97. 11%-98. 42%, respectively.The relative standard deviations(RSDs) of intermediate precision of TT, DT and DMAP were all less than 5%. The R~2 values of TT and DT were greater than 0. 999 0 in the range of 6-24 ??g/mL, and the R~2 value of DMAP was 1. 000 in the range of2-10 ??g/mL. The RSDs of TT, DT and DMAP content were all less than 3% at the injection temperature of 30, 35 and 40 ℃.The established method was used to determine the content of free proteins and DMAP in the test sample, and rapid and accurate results were obtained.Conclusion The established SEC-HPLC method has good system suitability, accuracy,precision, linear relationship and robustness, which can realize the dual quantification of free proteins and DMAP in the same experiment, and can be used to monitor the impurities in the binding process.

With the rapid development of the interdisciplinary area of artificial intelligence and medicine, large language model (LLM) has been widely used in the fields such as diagnosis and treatment, medicine, and healthcare. LLM has unique advantages in the field of traditional Chinese medicine (TCM), such as high consistency with the "Four Diagnostic Methods", perfect combination of natural language and self-supervised learning in TCM, the ability to adapt to the characteristics TCM formulas, and the assistance in TCM diagnosis and treatment. At present, various LLM models have been developed, including the "Qihuang Ask Big Model" and the Digital Traditional Chinese Medicine Big Model "GLM-130B", but they still face challenges such as value mismatch and medical abuse, increased demand for interpretability, lack of advanced technology, and domestic policy access. This article reviews the evolution of LLM, its unique advantages and applications in the field of TCM, the problems and challenges, and the future development trends, in order to providereference for the further promotion of LLM in traditional medicine.

"Target trial emulation" (TTE), as a new framework in real-world research, has been formally established in recent years. It can be used to guide the evaluation of the effectiveness and safety of medical interventions based on real-world data for observational causal inference. The core idea of this framework is to follow the principles of randomized controlled trial (RCT), emulate a corresponding RCT using real-world data, and then draw conclusions about the causal relationship between interventions and outcomes. The main implementation tips of TTE can be summarized as "3-7-2": 3 implementation steps including formulating the causal question, designing the emulation plan, and emulating the target study; 7 design elements including eligibility criteria, treatment strategies, intervention allocation, follow-up period, outcome, causal contrast of interest, and analysis plan; and control of 2 critical biases including immortal time bias and prevalent user bias. In this article, we present an overview of the development, current status, implementation steps, classic examples, advantages and limitations of TTE, and its application prospects in traditional Chinese medicine (TCM). It is hoped that this article can assist researchers in TCM to utilize this method for real-world research and contribute to the construction of a clinical evaluation system with distinctive features of TCM.