This paper summarized the clinical experience of Prof. LI Diangui in treating gastroesophageal reflux disease （GERD） based on the theory of turbidity-toxin in liver. It is believed that internal accumulation of turbidity-toxin and liver depression with stomach counterflow are the main pathogenesis of GERD， and thus the therapeutic methods of resolving turbidity and resolving toxins， regulating the liver and harmonizing the stomach are proposed. In clinical practice， GERD is divided into the early stage， middle stage and late stage. For the early stage， the modified Huazhuo Shugan Hewei Formula （化浊疏肝和胃方） is used to regulate qi and remove turbidity， soothe the liver and harmonize the stomach； for the middle stage， the modified Huazhuo Qingre Zhisuan Formula （化浊清热制酸方） is applied to clear heat， direct the turbid downward， and resolve toxins； for the late stage， the modified Yiwei Decoction （益胃汤） is adopted to replenish qi， nourish yin and simultaneously resolve turbidity-toxin. Throughout the treatment process， attention should be paid to protecting the spleen and stomach， and the medication could be modified according to changes of individual condition.

The prevalence of periodontitis in China is as high as 74.2%, making it the leading cause of tooth loss in adults and severely impacting both oral and overall health. The treatment of periodontitis and periodontal tissue regeneration are global challenges of significant concern. GE Shaohua' s group at School and Hospital of Stomatology, Shandong University has focused on the key scientific issue of "remodeling the periodontal inflammatory microenvironment and optimizing tissue repair and regeneration". They have elucidated the mechanisms underlying the persistence of periodontitis, developed bioactive materials to enhance stem cell regenerative properties, and constructed a series of guided tissue regeneration barrier membranes to promote periodontal tissue repair, leading to the establishment of a comprehensive technology system for the treatment of periodontitis. Specific achievements and progress include: (1) Elucidating the mechanism by which key periodontal pathogens evade antimicrobial autophagy, leading to inflammatory damage; developing intelligent antimicrobial hydrogels and nanosystems, and creating metal-polyphenol network microsphere capsules to reshape the periodontal inflammatory microenvironment; (2) Explaining the mechanisms by which nanomaterial structures and electroactive interfaces regulate stem cell behavior, developing optimized nanostructures and electroactive biomaterials, thereby effectively enhancing the regenerative repair capabilities of stem cells; (3) Creating a series of biphasic heterogeneous barrier membranes, refining guided tissue regeneration and in situ tissue engineering techniques, stimulating the body' s intrinsic repair potential, and synergistically promoting the structural regeneration and functional reconstruction of periodontal tissues. The research outcomes of the group have innovated the fundamental theories of periodontal tissue regeneration, broken through foreign technological barriers and patent blockades, established a cascade repair strategy for periodontal regeneration, and enhanced China' s core competitiveness in the field of periodontal tissue regeneration.
Humans ; Stem Cells/physiology* ; Periodontitis/therapy* ; Guided Tissue Regeneration, Periodontal/methods* ; Regeneration ; Biocompatible Materials ; Tissue Engineering/methods*

OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Objective To explore the predictive value of blood lipid dynamics of septic shock for the short-term prognosis.Methods A total of 107 patients with septic shock treated in Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine from March 2019 to July 2023 were selected as the study subjects.They were divided into survival group(n=76)and death group(n=31)based on their 28-day outcomes.Total cholesterol(TC),triacylglycerol(TG),high density lipoprotein cholesterol(HDL-C)and LDL cholesterol(LDL-C)concentrations were tested at disease onset(day 0),day 4±1 and day 7±1.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of lipid dynamics on outcomes in patients with septic shock.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of patients with septic shock.Result The levels of TC and HDL-C at disease onset,as well as TC,HDL-C and LDL-C on day(4±1)and day(7±1)in the survival group were higher than those in death group,and the differences were significant(Z=2.241～5.744,all P＜0.05).The areas under the curve[AUC(95％)]for the prediction of changes in HDL-C and LDL-C in the first week of admission were 0.775(95％CI:0.685～0.850)and 0.646(95％CI:0.547～0.736),with the best cutoff values of 0.16mmol/L and 0.28mmol/L,sensitivity of 70.97％and 64.52％,and specificity of 82.89％and 69.74％,respectively.Multivariate regression analysis showed that HDL-C dynamics was independently associated with poor prognosis(OR=0.141,95％CI:0.044～0.454,P=0.001).Conclusion Monitoring the dynamic changes of blood lipid at the first week of admission could help in predicting short-term outcomes in patients with septic shock.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Objective:To analyze the clinical and genetic characteristics of a child featuring Dias-Logan syndrome.Methods:A child with speech disorders and delayed psychomotor development from childhood who was admitted to the Rehabilitation Medicine Department of Children′s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the research subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Potential variant was screened by whole exome sequencing, and candidate variant was verified by Sanger sequencing. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011).Results:The child has presented with global developmental delay, microcephaly, special facial features and behavioral problems. Genetic testing revealed a de novo variant of the BCL11A gene, namely c. 561_567delACACGCA(p.Q187fs*7), which was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The heterozygous variant of BCL11A gene probably underlay the Dias-Logan syndrome in this child. Above finding has enriched the phenotypic and mutational spectrum of the BCL11A gene and provides a basis for genetic counseling and clinical decision-making.

Objective:To clarify the genetic diagnosis of two children with ring chromosome 18 and explore their mechanisms and clinical phenotypes.Methods:Two patients treated at the Children′s Hospital of Henan Province respectively in June 2022 and March 2023 were selected as the study subjects. Genetic testing and diagnosis were carried out through copy number variation sequencing (CNV-seq), G-banded chromosomal karyotyping, and whole exome sequencing (WES). This study was approved by the Children′s Hospital of Henan Province (Ethics No. 2023-K-075).Results:Child 1 had mainly manifested developmental delay, white matter hypoplasia, type 1 diabetes mellitus, and micropenis. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.21q22.1)[40]/46, XY[7], and CNV-seq results showed that he has a 14.86 Mb deletion at 18p11.21p11.32 and a 14.02 Mb deletion at 18q22.1q23. Child 2 had peculiar facial features, delayed white matter myelination, developmental delay, atrial septal defect, severe sensorineural deafness, and congenital laryngeal stridor. He was found to have a chromosomal karyotype of 46, XY, r(18)(p11.2q23). CNV-seq result proved that he had a 14.86 Mb deletion at 18p11.21p11.32 and a 20.74 Mb deletion at 18q21.32q23. WES has failed to detect single nucleotide variants (SNVs) in either child, but revealed a large segmental deletion at chromosome 18 in both of them.Conclusion:Both children were diagnosed with ring chromosome 18 syndrome. The different size of the deletional fragments in the 18q region and mosaicism of ring chromosome 18 in child 1 may underlay the variation in their clinical phenotypes. The type 1 diabetes mellitus and micropenis noted in both children are novel features for ring chromosome 18 syndrome.

Objective:To investigate the clinical and genetic features of the patient with neurodevelopmental disorders characterized by thickened corpus callosum caused by MAST1 gene mutation. Methods:Clinical data and auxiliary examination of a child with neurodevelopmental disorders caused by MAST1 gene mutation who was admitted to Henan Children′s Hospital in September 2022 were collected, and whole exome sequencing technology was applied to analyze the genetics of the child. Results:The patient was a 2 years and 8 months old male, with a clinical phenotype including intellectual, motor, and speech development disorders. Brain magnetic resonance imaging (MRI) showed thickened corpus callosum, nodular heterotopia of the left ventricle body.Whole exome sequencing showed the MAST1 gene with c.578T>G(p.Met193Arg) heterozygous missense variant, which was a unreported de novo pathogenic variant and both of his parents were wild-type. Conclusions:Diseases caused by MAST1 gene mutations are relatively rare, the main clinical features are neurodevelopmental disorders and brain structural abnormalities, and MRI shows an enlarged corpus callosum.The heterozygous missense variant c.578T>G(p.Met193Arg) of the MAST1 gene is the genetic cause of this case.

Objective:To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family.Methods:11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology.Results:All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia ( n = 7), cardiac malformation ( n = 2), elevated myocardial enzymes ( n = 4), hyperlipidemia ( n = 1), hyperkalemia ( n = 1), persistent diarrhea ( n = 3), developmental delay ( n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion:The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.