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.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.