OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Qingzao Jiufeitang is a famous classical formula for treating lung injury caused by warm and dryness， included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. By systematically organizing ancient and modern literature on this formula， this study analyzed and verified the origin， medicinal composition， original plants and processing， dosage and decoction method， efficacy and application of this formula. According to the research， Qingzao Jiufeitang was first recorded in Yimen Falyu in the Qing dynasty， and its creation was mainly inspired by the Ming dynasty physician MIAO Xiyong's idea of the moisturizing drugs with sweet flavour and cold nature. Based on the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia） and the textual research results of modern scholars on traditional Chinese herbal medicines， the botanical sources and processing methods of the herbs in this formula are basically clarified. Among them， Mori Folium， Gypsum Fibrosum， Ginseng Radix et Rhizoma， Sesami Semen Nigrum， Asini Corii Colla， Ophiopogonis Radix and Eriobotryae Folium are consistent with the 2020 edition of the Chinese Pharmacopoeia. The primary source of Glycyrrhizae Radix et Rhizoma is the dried roots and rhizomes of Glycyrrhiza uralensis， family Leguminosae， while the primary source of Armeniacae Semen Amarum is the dried mature seeds of Prunus armeniaca， family Rosaceae. It is recommended to use Gypsum Ustum， stir-fried Sesami Semen Nigrum， stir-fried Armeniacae Semen Amarum， Asini Corii Colla bead， and honey-fried Eriobotryae Folium， and the rest of the raw products. According to the conversion of ancient and modern doses， the recommended dosages are 11.19 g for Mori Folium， 9.33 g for Gypsum Fibrosum， 3.73 g for Glycyrrhizae Radix et Rhizoma， 2.61 g for Ginseng Radix et Rhizoma， 3.73 g for Sesami Semen Nigrum， 4.48 g for Ophiopogonis Radix， 2.61 g for Armeniacae Semen Amarum， 3.73 g for Eriobotryae Folium. The decoction method is to add 300 mL of water， decoct it down to 180 mL， remove the residue， and then add 2.98 g of Asini Corii Colla into the decoction. Take it warm after meals， two to three times a day. Qingzao Jiufeitang has the effects of clearing dryness and moistening the lungs， nourishing Yin and invigorating Qi. In ancient times， it was mainly used to treat stagnation and depression of various Qi， as well as paralysis， asthma and vomiting. In modern clinical practice， it is mostly used to treat diseases in respiratory system， otolaryngology， skin system and digestive system caused by warm-dry impairing lung， deficiency of both Qi and Yin. The above research results can provide a reference for the later development of Qingzao Jiufeitang.

Objective To investigate the risk factor for adverse events(AEs)after non-sedated esophagogastroduodenoscopy(EGD).Methods The data on clinical manifestations,adverse events after non-sedated EGD and common risk factors were collected and retrospectively analyzed with statistical methods in patients who underwent non-sedated EGD from May 2018 to June 2019.These patients were divided into AEs group and non-AEs group.Results Of 2 384 patients,57.67%(1 375/2 384)presented with nausea,12.79%(305/2 384)vomiting,and 5.79%(138/2 384)presented with pharyngalgia.Multivariate Logistic regression analysis was performed.Advanced age(≥65 years old)(OR=0.683,95%CI:0.506-0.921)was protective factors for nausea after non-sedated EGD.Hypertension(OR=1.361,95%CI:1.026-1.806),overweight(OR=1.399,95%CI:1.154-1.695),obesity(OR=2.594,95%CI:1.760-3.823)and inspection duration>15 min(OR=3.107,95%CI:2.296-4.206)were independent risk factors for nausea after non-sedated EGD.Advanced age(OR=0.393,95%CI:0.221-0.699)and imported equipment(OR=0.697,95%CI:0.546-0.890)were protective factors for vomiting after non-sedated EGD.Moreover,inspection duration>15 min(OR=1.641,95%CI:1.008-2.699)was independent risk factors for vomiting after non-sedated EGD.There was no difference in success rate of non-sedated EGD between two groups(P<0.05).Conclusion Hypertension,overweight and obesity were independent risk factors for nausea after non-sedated EGD.The advanced age and imported equipment were protective factors for vomiting after non-sedated EGD.In addition,inspection duration over 15 min is a risk factor for AEs such as nausea and vomiting after nonsedative EGD.Whether AEs occurred or not is non-related to success rate of non-sedated EGD.

Gastric cancer is a common clinical tumor,and its incidence and mortality rates rank among the top of malignant tumors.Helicobacter pylori(Hp)is an important carcinogenic factor for gastric cancer.Studies have found that in addition to Hp,other microorganisms in the stomach also play a key role in the progression of gastric cancer.The composition and diversity of the gastric microbiota vary significantly under different gastric disease conditions,which may affect the progression of gastric cancer.Hp can induce gastric epithelial inflammation and oxidative stress through various virulence factors,thereby promoting the occurrence of gastric cancer.Non-Hp microorganisms can be involved in the process of gastric cancer through pathways such as metabolic changes and immune regulation.In recent years,with the development of high-throughput sequencing technology,the complexity of gastric microbiota has gradually been revealed,which provides new insights for the early warning and intervention of gastric cancer.This article comprehensively review the role of gastric microbiota in the progression of gastric cancer.

Cancer ranks as the second leading cause of death globally and has surpassed cardiovascular diseases to become the primary cause of mortality in developed countries. Cancer stem cells (CSCs), which play crucial roles in cancer recurrence, metastasis, and drug resistance, have attracted significant attention in targeted therapeutic strategies. Aptamers, with unique three-dimensional structures capable of specifically recognizing the surface markers of CSCs, show promising potential in targeted drug delivery systems. Compared with conventional antibodies, aptamers are praised for small molecular weights, low production costs, and easy chemical modification. This review systematically summarizes recent advances in aptamer research targeting the surface markers of CSCs, with particular emphasis on aptamer-drug conjugate systems targeting the markers including EpCAM, CD133, CD44, and ABCG2. Both in vitro cellular studies and in vivo animal models have demonstrated the definite anti-cancer efficacy of aptamer-based drug delivery systems, which are of great significance to develop novel therapeutic strategies and improving the therapeutic effects of CSC-targeted treatment. Thus, aptamer-based drug delivery system has broad application prospects in the field of precise cancer treatment.
Humans ; Neoplastic Stem Cells/metabolism* ; Aptamers, Nucleotide/therapeutic use* ; Drug Delivery Systems/methods* ; Neoplasms/drug therapy* ; Biomarkers, Tumor/metabolism* ; Animals ; Epithelial Cell Adhesion Molecule ; AC133 Antigen ; Hyaluronan Receptors

Objective To investigate the risk factor for adverse events(AEs)after non-sedated esophagogastroduodenoscopy(EGD).Methods The data on clinical manifestations,adverse events after non-sedated EGD and common risk factors were collected and retrospectively analyzed with statistical methods in patients who underwent non-sedated EGD from May 2018 to June 2019.These patients were divided into AEs group and non-AEs group.Results Of 2 384 patients,57.67%(1 375/2 384)presented with nausea,12.79%(305/2 384)vomiting,and 5.79%(138/2 384)presented with pharyngalgia.Multivariate Logistic regression analysis was performed.Advanced age(≥65 years old)(OR=0.683,95%CI:0.506-0.921)was protective factors for nausea after non-sedated EGD.Hypertension(OR=1.361,95%CI:1.026-1.806),overweight(OR=1.399,95%CI:1.154-1.695),obesity(OR=2.594,95%CI:1.760-3.823)and inspection duration>15 min(OR=3.107,95%CI:2.296-4.206)were independent risk factors for nausea after non-sedated EGD.Advanced age(OR=0.393,95%CI:0.221-0.699)and imported equipment(OR=0.697,95%CI:0.546-0.890)were protective factors for vomiting after non-sedated EGD.Moreover,inspection duration>15 min(OR=1.641,95%CI:1.008-2.699)was independent risk factors for vomiting after non-sedated EGD.There was no difference in success rate of non-sedated EGD between two groups(P<0.05).Conclusion Hypertension,overweight and obesity were independent risk factors for nausea after non-sedated EGD.The advanced age and imported equipment were protective factors for vomiting after non-sedated EGD.In addition,inspection duration over 15 min is a risk factor for AEs such as nausea and vomiting after nonsedative EGD.Whether AEs occurred or not is non-related to success rate of non-sedated EGD.

Gastric cancer is a common clinical tumor,and its incidence and mortality rates rank among the top of malignant tumors.Helicobacter pylori(Hp)is an important carcinogenic factor for gastric cancer.Studies have found that in addition to Hp,other microorganisms in the stomach also play a key role in the progression of gastric cancer.The composition and diversity of the gastric microbiota vary significantly under different gastric disease conditions,which may affect the progression of gastric cancer.Hp can induce gastric epithelial inflammation and oxidative stress through various virulence factors,thereby promoting the occurrence of gastric cancer.Non-Hp microorganisms can be involved in the process of gastric cancer through pathways such as metabolic changes and immune regulation.In recent years,with the development of high-throughput sequencing technology,the complexity of gastric microbiota has gradually been revealed,which provides new insights for the early warning and intervention of gastric cancer.This article comprehensively review the role of gastric microbiota in the progression of gastric cancer.

Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.

Background and Aims:Chronic skin ulcers are a significant disease affecting patients'daily lives and psychological well-being.Abnormalities in the cells and extracellular matrix within the tissue may disrupt the balance of the microenvironment,hindering the normal skin repair process and leading to delayed healing of the ulcer.There is currently a lack of research on the mechanisms underlying the development of chronic ulcers and their diagnostic biomarkers.Single-cell sequencing,a newly developed high-throughput sequencing method in recent years,uses gene sequencing at the single-cell resolution to precisely reveal disease mechanisms and has been applied in various diseases.This study used single-cell transcriptome sequencing(scRNA-Seq)to investigate the cellular heterogeneity in chronic skin ulcer tissue to elucidate the potential molecular mechanisms behind delayed healing and provide new insights for clinical treatment.Methods:The scRNA-Seq technology was used to compare the differences in cell subpopulations and gene expression between chronic ulcer tissue and normal skin tissue.Single cells were sorted using a microfluidic platform,and cDNA libraries were constructed for subsequent differential gene analysis and functional enrichment analysis.Results:scRNA-Seq analysis revealed significant immune-metabolic remodeling features in chronic ulcer tissue:the number of B cells,monocytes,and macrophages in ulcer tissue increased by 2.1 to 3.5 times compared to the normal tissue control.This was accompanied by widespread activation of collagen synthesis genes(COL1A1/COL3A1)and synergistic suppression of immune regulators(e.g.,granzyme family GZMA/GZMB/H).Cross-cell subpopulation functional network analysis showed that hypoxia response mediated by the HIF-1 signaling pathway and PI3K/Akt pathway abnormalities formed a positive feedback loop,exacerbating the imbalance in the secretion of inflammatory factors(CXCL3/8,TGFBI)and compensatory upregulation of mitochondrial oxidative phosphorylation.Conclusion:Chronic skin ulcers exhibit significant differences in cellular heterogeneity and gene expression,suggesting that chronic ulcers are not simply tissue defects but a complex pathological process dominated by chronic inflammation and immune dysregulation.The coordinated dysregulation of multiple cell subpopulations in the ulcer microenvironment,along with persistent inflammatory responses and metabolic abnormalities,is interconnected through the HIF-1/TNF/MAPK pathway network.Downregulation of granzyme gene family members and abnormal histone modifications may contribute to immune clearance defects,providing a theoretical basis for developing novel therapies targeting epigenetic regulation or mitochondrial function.