OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

Objective To establish a nomogram prediction model of hyperuricemia(HUA)onset risk in overweight and obese children and adolescents in order to provide reference for the prevention and treatment of HUA in this population.Methods The clinical data of 1 410 overweight and obese children and adolescents aged 6-17 years old visiting in this hospital from September 2021 to August 2022 were retrospectively analyzed.A total of 987 overweight and obese children and adolescents were randomly extracted according to a ratio of 7:3 to establish the model,and the remaining 423 cases were validated internally.Referring to the definition of high uric acid in"Zhu-futang Practical Pediatrics",the subjects were divided into high uric acid group and non-high uric acid group.The logis-tic regression analysis was used to analyze the influencing factors of HUA in overweight and obese children and adoles-cents.The nomogram model was constructed by using the R language.The area under the receiver operating character-istic(ROC)curve(AUC),decision analysis curve(DIC),clinical impact curve(CIC)and C-index were used to evalu-ate the predictive ability of the model,and the Bootstrap repeated sampling method(taking samples for 1000 times)was used for internal validation of the model.Results The results of multivariate analysis showed that the age(OR=2.324,95％CI:1.155-4.672,P=0.018),gender(OR=0.456,95％CI:0.256-0.810,P=0.007),triglycerides(OR=3.775,95％CI:2.321-6.138,P＜0.001),blood calcium(OR=26.986,95％CI:3.186-228.589,P=0.003)and blood creatinine(OR=1.047,95％CI:1.026-1.070,P＜0.001)were the influen-cing factors of HUA in overweight and obese children and adolescents.AUC of the ROC curve of the model was 0.840,the sensitivity was 0.786,the specificity was 0.762,the Youden index was 0.548,and the C-index was 0.840.The risk probability of DC A was 0.1-0.8,the net benefit rate of both models was＞0,AUC of ROC curve in the internal verification was 0.871.Conclusion The constructed nomogram in this study has a good predictive efficiency for the onset risk of HUA in overweight and obese children and adolescents,and may provide reference for the early diagnosis and treatment of this population.

Objective To compare the effectiveness and safety of semaglutide with dulaglutide in patients diagnosed with type 2 diabetes.Methods A multicenter retrospective cohort study was conducted to include patients with type 2 diabetes who received semaglutide or dulaglutide treatment at three hospitals between April 2021 and July 2023 in the study.The patients were divided into the semaglutide group(SEMA group)and the dulaglutide group(DULA group)based on their treatment.Propensity score matching was used to pair the two groups in a 1:1 ratio,aligning them based on baseline characteristics such as gender,age,body mass index,blood glucose levels,duration of diabetes,and complications.Various parameters including fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum creatinine,urea nitrogen levels,estimated glomerular filtration rate(eGFR),urinary albumin/creatinine ratio(UACR),and occurrences of adverse reactions were assessed at 3,6,9,and 12 months after the treatment.Results After propensity score matching,98 patients were included in both the SEMA and DULA groups,showing no statistically significant differences in baseline characteristics between the groups(P＞0.05).At each follow-up point,the fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels of both groups showed a significant decrease compared to the baseline(P≤0.05).The inter-group comparison revealed no statistically significant differences in the changes in fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels between the two groups(P＞0.05).At the 6th month,the SEMA group exhibited a statistically significant higher rate of HbA1c＜7％compared to the DULA group(P＜0.05).In the SEMA group,serum creatinine and urea nitrogen decreased significantly at the 6th month compared to baseline,while eGFR showed an increase at the 3rd and 6th month,and UACR decreased,all with statistical significance(P＜0.05).In the DULA group,there was a statistically significant increase in serum creatinine and decrease at the 3rd and 6th months in eGFR,respectively.Additionally,urea nitrogen levels decreased significantly at the 9th month,all differences were statistically significant(P＜0.05).The inter-group comparison revealed that at the 3rd and 6th month,the SEMA group exhibited a greater reduction in serum creatinine levels compared to the DULA group.Additionally,the SEMA group demonstrated a more pronounced increase in eGFR levels than the DULA group,with statistical significance(P＜0.05).At the 6th month,the SEMA group exhibited a significantly greater decrease in UACR and a significantly lower incidence of renal insufficiency compared to the DULA group(P＜0.05).There were no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Semaglutide and dulaglutide can significantly improve blood glucose control,exhibit comparable effectiveness and safety in lowering blood glucose levels,and semaglutide has a potentially protective effect on renal function.

Objective To construct a rehabilitation nursing program for stroke patients based on the international classification of functioning, disability and health (ICF). Methods The relevant domestic and foreign literatures were systematically searched, and a draft of the rehabilitation nursing program for stroke patients based on the 17 functional items in the four dimensions of ICF functional evaluation was constructed. The Delphi method was used to consult experts to further improve the program. Results A total of 16 experts completed two rounds of expert consultation. The expert authority coefficients of the first and second rounds of consultation were 0.897 and 0.897, respectively, with coefficient of variations ranging from 0.05 to 0.27 and 0.05 to 0.19, respectively. The Kendall's W coefficients were 0.384 and 0.452 (χ²=104.375, 122.831, P < 0.001), respectively. In the final rehabilitation nursing program for stroke patients, there were four first-level indicators (functional domains), 17 second-level indicators (intervention contents), and 73 third-level indicators (specific measures). Conclusion The rehabilitation nursing program for stroke patients based on ICF is scientific and reliable, and may provide theoretical support and practical guidance for the rehabilitation nursing of clinical stroke patients.

ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg^-1·d^-1），and hydroxychloroquine （HCQ） group （1.30 g·kg^-1·d^-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.

ObjectiveTo observe the efficacy and safety of Huashi Runzao prescription for patients with primary Sjögren's syndrome （pSS） of combined dryness and dampness pattern. MethodA total of 105 eligible patients were randomized into the experimental group （65 cases） and control group （40 cases）， and they were respectively treated with Huashi Runzao prescription and hydroxychloroquine for 12 weeks. Visual Analogue Scale （VAS） was employed to assess the symptoms. The symptoms of dryness， fatigue， and pain， European League Against Rheumatism （EULAR） Sjögren's Syndrome Patient Reported Index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， and immune inflammatory indicators before and after treatment were compared between the two groups， and adverse reactions were observed. ResultAfter treatment， the ESSPRI score was lower than that before treatment in the experimental groups （P<0.01） and was lower in the experimental group than in the control group （P<0.05）. The VAS scores of dry mouth， dry eyes， overall dryness， fatigue， and pain in the experimental group decreased compared with those before treatment （P<0.01）， and the experimental group had lower VAS scores of dry mouth and overall dryness than the control group （P<0.01）. After treatment， the ESSDAI score of both groups decreased compared with that before treatment （P<0.05， P<0.01）， but there was no significant difference between the groups. After treatment， the level of immunoglobulin M （IgM） decreased （P<0.01） and the level of complement C3 increased （P<0.01） in the experimental group， while the level of complement C3 decreased in the control group （P<0.05）. There was no significant difference in the laboratory indexes between groups. During the treatment， stomachache occurred to one case in the experimental group， which was alleviated after the treatment， and no adverse reaction was observed in the control group. According to the chi-square test， the occurrence of adverse reactions was insignificantly different between the two groups. ConclusionHuashi Runzao prescription can alleviate the symptoms of dryness， fatigue， and pain， and reduce disease activity without associated side effects in pSS patients with combined dampness and dryness pattern.

ObjectiveTo summarize the characteristics of traditional Chinese medicine （TCM） syndrome in primary Sjögren's syndrome （pSS） patients with interstitial lung disease （ILD） and to explore associated factors. MethodA survey was conducted and pSS patients who were treated in TCM department of rheumatism at China-Japan Friendship Hospital from December 2018 to April 2022 were included. Tongue manifestations and syndromes of patients were recorded. pSS patients with ILD were classified into the pSS-ILD group and those without the ILD were included in the pSS-non-ILD group. The tongue manifestations， syndromes， and laboratory indexes were compared between the two groups， and logistic regression was used to explore the factors associated with pSS-ILD. ResultA total of 200 pSS patients were included， with 186 （93.0%） females， median age of 57 years， and median disease course of 60 months， of which 44 （22%） had pSS-ILD. In terms of tongue manifestations， pSS-ILD patients generally had dark/purple/stasis tongue， fissured tongue， and tongue with little fluid， thick coating， yellow coating， and greasy coating. The proportion patients with yellow coating was higher in pSS-ILD group than in the pSS-non-ILD group （χ²=4.799，P<0.05）. In terms of syndrome， more than 40% of pSS-ILD patients had Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. As for Yin deficiency， liver-kidney Yin deficiency syndrome ranked the first. For Qi deficiency， lung Qi deficiency syndrome was most commonly seen. The proportion of patients with lung Qi deficiency was higher in the pSS-ILD group than in the pSS-non-ILD group （χ²=18.667，P<0.01）. As to laboratory indexes， compared with the pSS-non-ILD group， pSS-ILD group had high proportion of anti-SSA-positive patients （P<0.05） and high levels of C-reactive protein （CRP） （P<0.01）， complement C3 （χ²=4.332，P<0.05）， and complement C4 （P<0.05）. Logistic regression analysis showed that pSS with ILD was positively associated with lung Qi deficiency ［odds ratio （OR）=6.079， 95% confidence interval （CI） 2.585-14.298， P<0.01）］ and yellow coating （OR=5.260， 95% CI 1.337-20.692， P<0.05） and negatively associated with low C4 （OR=0.199， 95% CI 0.070-0.564， P<0.01）. ConclusionAbout 22% of pSS patients had ILD， and patients with pSS-ILD generally have Qi deficiency， Yin deficiency， phlegm-dampness， Qi stagnation， and/or blood stasis syndrome. Yellow coating， lung Qi deficiency and C4 level are factors associated with pSS combined with ILD.

OBJECTIVE: The prepare decellularized extracellular matrix (ECM) scaffold materials derived from human cervical carcinoma tissues for 3D culture of cervical carcinoma cells. METHODS: Fresh human cervical carcinoma tissues were treated with sodium lauryl ether sulfate (SLES) solution to prepare decellularized ECM scaffolds. The scaffolds were examined for ECM microstructure and residual contents of key ECM components (collagen, glycosaminoglycan, and elastin) and genetic materials by pathological staining and biochemical content analysis. In vitro 3D culture models were established by injecting cultured cervical cancer cells into the prepared ECM scaffolds. The cells in the recellularized scaffolds were compared with those in a conventional 2D culture system for cell behaviors including migration, proliferation and epithelial-mesenchymal transition (EMT) wsing HE staining, immunohistochemical staining and molecular biological technology analysis. Resistance to 5-fluorouracil (5-Fu) of the cells in the two culture systems was tested by analyzing the cell apoptosis rates via flow cytometry. RESULTS: SLES treatment effectively removed cells and genetic materials from human cervical carcinoma tissues but well preserved the microenvironment structure and biological activity of ECM. Compared with the 2D culture system, the 3D culture models significantly promoted proliferation, migration, EMT and 5-Fu resistance of human cervical cancer cells. CONCLUSION The decellularized ECM scaffolds prepared using human cervical carcinoma tissues provide the basis for construction of in vitro 3D culture models for human cervical cancer cells.
Female ; Humans ; Decellularized Extracellular Matrix ; Extracellular Matrix ; Uterine Cervical Neoplasms ; Tissue Scaffolds/chemistry* ; Carcinoma ; Fluorouracil/pharmacology* ; Tissue Engineering ; Tumor Microenvironment

Cell metabolomics is an important branch of metabolomics, which could dynamically monitor cell response and metabolic changes after drugs acting on cells, and look for potential biomarkers. Cell metabolomics has been widely used in illustration of disease mechanism, evaluation of drug efficacy and development of new drug through elucidating the pathophysiological mechanism of the disease and the effect of drug treatment intervention. The researches process of cellular metabolomics and its application in central nervous system diseases were reviewed in order to provide theoretical basis for in-depth study of the pathogenesis and prevention and treatment of central nervous system diseases.

Objective To investigate the value of international standardized ratio-to-platelet ratio (INPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis in patients with primary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were diagnosed with PBC in The First Affiliated Hospital of Zhengzhou University from October 2013 to March 2021. Scheuer score was used to systematically evaluate the degree of liver fibrosis (S0-S4 stage). According to the results of liver biopsy, the degree of liver fibrosis was classified as significant liver fibrosis (≥S2), progressive liver fibrosis (≥S3), and liver cirrhosis (S4). Related data including general information, liver function, routine blood test results, and blood coagulation were collected, and related formulas were used to calculate the values of the noninvasive serological models INPR, APRI, and FIB-4. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. A Spearman correlation analysis was used to evaluate the correlation between noninvasive models and liver fibrosis stage. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the noninvasive serological models in the diagnosis of liver fibrosis degree, and the DeLong method was used for comparison of the area under the ROC curve (AUC). Results A total of 143 patients with PBC were enrolled in the study, among whom 4 had stage S0 liver fibrosis, 50 had stage S1 liver fibrosis, 46 had stage S2 liver fibrosis, 26 had stage S3 liver fibrosis, and 17 had stage S4 liver fibrosis. There was a significant difference in INPR value between the PBC patients with different liver fibrosis degrees ( χ 2 =27.347, P < 0.001). INPR value gradually increased with the aggravation of liver fibrosis degree, and INPR was positively correlated with liver fibrosis degree ( r =0.419, P < 0.01). The ROC curve analysis showed that INPR, APRI, and FIB-4 had an AUC of 0.691, 0.706, and 0.742, respectively, in the diagnosis of significant liver fibrosis (≥S2) in PBC patients, at the corresponding cut-off values of 0.63, 0.59, and 2.68, respectively. INPR, APRI, and FIB-4 had an AUC of 0.731, 0.675, and 0.756, respectively, in the diagnosis of progressive hepatic fibrosis (≥S3) in PBC patients, at the corresponding cut-off values of 0.64, 1.23, and 4.63, respectively. INPR, APRI, and FIB-4 had an AUC of 0.820, 0.786, and 0.818, respectively, in the diagnosis of liver cirrhosis (S4) in PBC patients, at the corresponding cut-off values of 0.95, 1.26, and 4.63, respectively. In the evaluation of significant liver fibrosis, progressive liver fibrosis, and liver cirrhosis, there was no significant difference in AUC between INPR and APRI/FIB-4 (all P > 0.05). Conclusion INPR is a simple and accurate noninvasive model for the evaluation of liver fibrosis and has a certain value in the diagnosis of liver fibrosis in PBC.