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

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.

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.

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.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Breast cancer is one of the most common malignant tumors among women worldwide, with an increasing incidence rate year by year, making it a significant public health concern. With the continuous advancement of tumor biology research, N 6-methyladenosine (m 6A) modification, as an important form of RNA modification, has attracted growing attention. The m 6A modification, the most prevalent RNA modification in eukaryotes, occurs in almost all types of RNA and plays a critical role in the occurrence, progression, and metastasis of breast cancer. It influences cell proliferation, apoptosis, and alterations in the tumor microenvironment, though the specific mechanisms underlying these effects require further in-depth investigation. Moreover, the specific patterns of m 6A modification demonstrate its potential as a novel biomarker for breast cancer, which could provide new directions for early diagnosis and prognosis evaluation.

Objective:To establish a quality standard system for Descurainiae Semen under the requirements of German Pharmaceutical Codex (DPC); To compare the similarities and differences between DPC and the Pharmacopoeia of the People's Republic of China regarding the establishment of a quality standard system for TCM medicinal materials. Methods:Based on the requirements of DPC, and referring to the relevant methods of Pharmacopoeia of the People's Republic of China, the quality of 30 batches of Descurainiae Semen samples were assessed by observing the appearance and microscopic characteristics and determining their loss on drying, total ash content, and ash insoluble in hydrochloric acid. A TLC identification method was established based on a silica gel G TLC plate, using a developing agent composed of ethyl acetate, formic acid, and water in the ratio of 7:1.5:2.5 ( V/ V/ V). The method utilized rutin and quercetin as indicators for the System Suitability Test (SST), and took quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside and isorhamnetin 3-O-β-D-glucose-7-O-β-D-gentiobioside as the index. Based on the content determination method for Descurainiae Semen in the Pharmacopoeia of the People's Republic of China, a content determination method was established with quercetin-3-O-β-D-glucose-7-O-β- D-gentiobioside as the index. Results:The loss on drying for the 30 batches of samples ranged from 6.15% to 12.0%, with the total ash content ranged from 3.17% to 9.44%, and the ash insoluble in hydrochloric acid content ranged from 0.14% to 4.82%. The resolution of rutin and quercetin met the DPC's requirements for the SST criteria in TLC identification, and all batches of samples showed good separation of the index components. This method could effectively distinguish Descurainiae Semen from Lepidii Semen. Using modern chromatographic and spectroscopic techniques, the structure of the chromatographic peak adjacent to the component of the index (quercetin-3-O-β- D-glucoside-7-O-β-D-gentiobioside) was identified as descuraic anhydride B. The resolution between the two components in all batches of samples was greater than 3.1, which met the DPC's requirements for the SST criteria in content determination. The results of the methodological investigations met the requirements for content determination. The content of quercetin-3-O-β- D-glucose-7-O-β-D-gentiobioside in 30 batches of samples ranged from 0.062%-0.125%.Conclusion:The established quality standard system for Descurainiae Semen in this article is comprehensive, and meets the requirements of the DPC, which can be used for the quality control of Descurainiae Semen.