Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

SkinPro Ointment is an emulsion-based preparation derived from a traditional Tibetan medical empirical formula and developed using modern pharmaceutical technology. It is an exclusive patented product of Tibet Hairong Tangguo Pharmaceutical Co. Ltd. and has been listed as a National Protected Traditional Chinese Medicine Variety， the Pharmacopoeia of the People's Republic of China， and classified as a Category B product in the National Basic Medical Insurance Catalog. The ointment possesses the functions of clearing heat and drying dampness， activating blood circulation and dispelling wind， relieving itching and reducing inflammation. Clinically， it is used for skin pruritus caused by dampness-heat accumulation or blood-heat with wind-dryness， as well as pruritic skin diseases such as neurodermatitis， eczema， tinea pedis， and psoriasis. To clarify the standards for its clinical application and promote rational drug use， a consensus working group comprising 34 national experts in dermatology， evidence-based medicine， and pharmacy was established. Through expert interviews， the nominal group technique， and questionnaire surveys， 15 clinical issues were identified. The Grading of Recommendations Assessment， Development and Evaluation （GRADE） evidence grading system was employed to assess the quality of evidence， leading to the formulation of the Expert Consensus on the Clinical Application of SkinPro Ointment. This consensus specifies that the intended users are physicians and pharmacists in medical institutions at all levels. It standardizes the clinical application of the ointment， including syndrome characteristics， dosage and course of treatment， combination therapy， precautions， and contraindications. Recommendations and consensus suggestions were formed addressing the 15 clinical issues， covering the following key areas： ①Indications and TCM syndromes： In TCM， the ointment mainly treats conditions such as "damp sores" （Shichuang）， "white scaling" （Baibi）， "collar sores" （Shelingchuang）， and "damp foot Qi" （Jiaoshiqi）， corresponding to eczema， psoriasis， neurodermatitis， and tinea pedis in Western medicine. The relevant TCM syndromes are identified as dampness-heat accumulation or blood-heat with wind-dryness. ②Usage and dosage： For external use， apply to the affected area 3 times daily. The dosage should follow the fingertip unit （FTU） principle. A treatment course of 1-2 weeks is recommended for mild to moderate cases； for serious cases， the course should be followed as prescribed by a physician. ③Combined therapy： The ointment can be used as monotherapy for mild cases. For moderate to severe cases， combination therapy is recommended， with reference to relevant clinical guidelines. ④Safety： Common adverse reactions include skin rashes， pruritus， and erythema. The ointment is contraindicated in patients with broken skin or obvious exudation at the affected area， as well as in patients with known hypersensitivity to any of its components. Contact with sensitive areas such as the eyes and oral mucosa should be avoided. Modern research shows that the ointment also has potential efficacy in other dermatological conditions， such as adult atopic dermatitis， tinea cruris， exfoliative keratolysis， acne vulgaris， and Malassezia folliculitis. This consensus provides a scientific basis for promoting the rational clinical use of SkinPro Ointment， improving its therapeutic efficacy， and reducing medication risks. Future updates will be dynamically revised according to emerging clinical issues and new evidence.

ObjectiveTo explore the construction of a machine learning model for the diagnosis of traditional Chinese medicine （TCM） syndromes in chronic cough and the optimization of this model using the Voting ensemble algorithm. MethodsA retrospective analysis was conducted using clinical data from 921 patients with chronic cough treated at the Respiratory Department of Dongfang Hospital， Beijing University of Chinese Medicine. After standardized processing， 84 clinical features were extracted to determine TCM syndrome types. A specialized dataset for TCM syndrome diagnosis in chronic cough was formed by selecting syndrome types with more than 50 cases. The synthetic minority over-sampling technique （SMOTE） was employed to balance the dataset. Four base models， logistic regression （LR）， decision tree （dt）， multilayer perceptron （MLP）， and Bagging， were constructed and integrated using a hard voting strategy to form a Voting ensemble model. Model performance was evaluated using accuracy， recall， precision， F1-score， receiver operating characteristic （ROC） curve， area under the curve （AUC）， and confusion matrix. ResultsAmong the 921 cases， six syndrome types had over 50 cases each， phlegm-heat obstructing the lung （294 cases）， wind pathogen latent in the lung （103 cases）， cold-phlegm obstructing the lung （102 cases）， damp-heat stagnating in the lung （64 cases）， lung yang deficiency （54 cases）， and phlegm-damp obstructing the lung （53 cases）， yielding a total of 670 cases in the specialized dataset. High-frequency symptoms among these patients included cough， expectoration， odor-induced cough， throat itchiness， itch-induced cough， and cough triggered by cold wind. Among the four base models， the MLP model showed the best diagnostic performance （test accuracy： 0.9104； AUC： 0.9828）. Compared with the base models， the Voting ensemble model achieved superior performance with an accuracy of 0.9289 on the training set and 0.9253 on the test set， showing a minimal overfitting gap of 0.0036. It also achieved the highest AUC （0.9836） in the test set， outperforming all base models. The model exhi-bited especially strong diagnostic performance for damp-heat stagnating in the lung （AUC： 0.9984） and wind pathogen latent in the lung （AUC： 0.9970）. ConclusionThe Voting ensemble algorithm effectively integrates the strengths of multiple machine learning models， resulting in an optimized diagnostic model for TCM syndromes in chronic cough with high accuracy and enhanced generalization ability.

Objective:This study aims to investigate the influence of microvessel density（MVD） and microlymphatic vessel density（MLVD） on the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to develop a nomogram prediction model for prognosis based on pathological characteristics. Methods:A retrospective analysis was conducted on clinicopathological and follow-up data from HPSCC patients who underwent surgical treatment at our institution between June 2010 and June 2020. Immunohistochemical staining was performed on tumor tissues and adjacent normal margin tissues to evaluate MVD and MLVD. The associations among MVD, MLVD, and clinicopathological features were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors affecting overall survival（OS）. Based on these findings, a nomogram model was constructed and its predictive accuracy was assessed using C-index, receiver operating characteristic（ROC） curve, and calibration curve. Results:Both MVD and MLVD were significantly higher in HPSCC tumor tissues compared to normal tissues. Patients in the high MVD and high MLVD groups exhibited significantly lower OS rates than those in the low MVD and low MLVD groups. Multivariate Cox regression analysis revealed that N stage, recurrence, nerve invasion, lymph node capsule invasion, MVD, and MLVD were independent prognostic factors of OS. Based on these factors, a nomogram prognosis model was successfully constructed. The nomograms demonstrated superior performance in terms of C-index, area under the ROC curve, and calibration, outperforming the AJCC TNM staging system. Conclusion:Elevated MVD and MLVD levels are associated with poorer prognosis in HPSCC patients. The nomogram model based on pathological features provides valuable insights for clinical assessment and decision-making.
Humans ; Hypopharyngeal Neoplasms/blood supply* ; Prognosis ; Retrospective Studies ; Microvascular Density ; Nomograms ; Lymphatic Vessels/pathology* ; Male ; Female ; Middle Aged ; Carcinoma, Squamous Cell/blood supply* ; Microvessels/pathology* ; Lymphatic Metastasis ; Survival Rate

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

OBJECTIVE To explore the effects of dihydroartemisinin(DHA)on the functions of cancer-associated fibroblasts(CAFs)in the tumor microenvironment in hypopharyngeal squamous cell carcinoma(HPSCC).METHODS The influence of conditioned media from CAFs and normal fibroblasts(NFs)on tube formation was assessed using a tube formation assay.Secreted protein levels of IL-6,VEGFA,and VEGFC were measured by immunofluorescence and ELISA.Western blotting was used to evaluate the expression of α-SMA,p-STAT3,STAT3,VEGF-A,and VEGF-C within the STAT3 signaling pathway.After treatment with DHA,the optimal concentration for DHA's effect was determined using CCK8 assays and morphological observations of cells.The impact of DHA on angiogenesis was analyzed through tube formation assays,changes in IL-6 expression were detected using ELISA and immunofluorescence,and alterations in α-SMA,p-STAT3,and STAT3 expression were examined by Western blot.RESULTS Both CAFs and NFs exhibited pro-angiogenic and pro-lymphangiogenic effects,with CAFs showing a more pronounced impact.Activated CAFs overexpressed and secreted high levels of IL-6,VEGF-A,and VEGF-C.The concentration of IL-6 in the conditioned medium supernatants of CAF1 and CAF2 was significantly higher than that of NF1 and NF2(P1<0.001,P2<0.05).Similarly,the concentration of VEGF-A was significantly increased(P1<0.05,P2<0.01),and the concentration of VEGF-C was also significantly increased(P1<0.05,P2<0.01).Treatment with DHA inhibited the activated state of CAFs,reducing the expression and secretion of IL-6 and p-STAT3,thereby suppressing tube formation.CONCLUSION Our findings indicate that CAFs promote angiogenesis and lymphangiogenesis in HPSCC via activation of the STAT3 pathway.DHA effectively inhibits this process,suggesting a potential new therapeutic strategy for the treatment of HPSCC.

Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.