BACKGROUND:Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts.However,there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS:The human periodontal ligament stem cells were isolated and cultured.Passage 3 cells were selected and treated with ordinary medium containing different concentrations(0,1,2,4,6,8 μmol/L)of ursolic acid.After intervention for 1,3,5,7 days,the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened.Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0,1,2,4 μmol/L ursolic acid,respectively.After 7 days of intervention,the mRNA expressions of alkaline phosphatase,Runx2,and osteocalcin were detected by qRT-PCR.After 14 days of intervention,the formation of mineralized nodules was observed by alizarin red staining.Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution;the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid(2 μmol/L)and the bone morphogenetic protein signaling pathway antagonist Noggin,respectively.The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid(2 μmol/L)and Noggin,the inhibitor of bone morphogenetic protein signaling pathway,and cultured for 7 days.qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2. RESULTS AND CONCLUSION:(1)1,2,4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells.6,8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells,and 1,2,4 μmol/L ursolic acid was selected to intervene in subsequent experiments.(2)Compared with 0 μmol/L,1,2,4 μmol/L ursolic acid could promote the expression of alkaline phosphatase,Runx2,and osteocalcin mRNA and the formation of mineralized nodules(P<0.05),and the effect of 2 μmol/L ursolic acid was the most significant.(3)Compared with the control group,the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2 in the ursolic acid group were increased(P<0.05),while mRNA and protein expressions of the above indexes were decreased in the antagonist group(P<0.05).Compared with the ursolic acid group,mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group(P<0.05).(4)The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.

Objective To review the research on the application of clinical decision support system(CDSS)involving nurses in depression both domestically and internationally.Methods 10 Chinese and English databases including PubMed,Web of Science,Scopus,CINAHL,PsycINFO,Embase,Cochrane Library,CNKI,Wanfang Database,and VIP were searched until March,2024.The eligible literature of the application of CDSS involving nurses in depression was selected to analyze the basic characteristics of studies,the functions,characteristics,feasibility,and effectiveness of CDSS.Results Finally,16 English articles involving 13 CDSS were included.This study found that nurses participating in CDSS can improve the degree of depression in patients,but its application in depression management is mainly for screening,and few CDSS can propose personalized depression management programs based on the psychological and social factors of patients.Conclusion The CDSS involving nurses can promote the screening of depression and improve depression in patients,but it fails to propose a personalized depression management program.Future research can develop CDSS based on electronic medical record systems to facilitate nurses'screening for depression and further develop an intelligent management module for CDSS to provide intelligent and personalized management solutions for patients with depression.

Objective:To explore the application effect of intelligent referral mode in examinees with major positive results in physical examinations in a health medical center.Methods:A cross-sectional study was conducted from January 2022 to December 2023 with subjects receiving physical examinations. Those subjects with major positive results from January 2022 to December 2022 in the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University were selected as the routine referral group, and those with major positive results from January 2023 to December 2023 were selected as the intelligent referral group. The routine referral group received routine health education from the chief inspector in the health medical center, suggesting them to get outpatient consultation. On the basis of ordinary referral, the intelligent referral group received health education from a referral team composed of nurses and specialists based on internet technology to digitally integrate and share patients′ medical records, examination results, imaging data and other medical information. The subects in the intelligent referral group were provided with a green channel for outpatient consultation and medical treatment immediately. The visiting rate, hospitalization rate, average visiting time, and overall satisfaction of the subjects after being notified of abnormal results were compared between the two groups. According to the positive results, the subjects were divided into four subgroups: ultrasound examination group, radiology group, clinical laboratory group and blood pressure group.Results:After the notification, there were significant differences in hospital visit rate (84.8% vs 67.2%, χ 2=168.4), hospitalization rate (48.8% vs 36.5%, χ 2=17.80), average visit time (116 min vs 301 min, Z=-15.82), and overall satisfaction score (9.70±0.62 vs 8.29±1.26, t=-33.47) between intelligent referral group and general referral group (all P<0.01). The classification statistics of major abnormal results showed that the consultation rates in subjects with ultrasound, radiology, clinical laboratory and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (87.9% vs 70.4%, 89.9% vs 70.6%, 80.6% vs 60.2%, 57.2% vs 41.3%, respectively; χ 2=41.91, 39.37, 19.37, 6.20, all P<0.05); the hospitalization rates in subjects with ultrasound, radiology and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (66.8% vs 64%, 55.7% vs 42.2%, 18.7% vs 11.2%, respectively; χ 2=16.86, 11.91, 8.68, all P<0.05); the mean consultation times in subjects with ultrasound, radiology and clinical laboratory abnormities in the intelligent referral group were all significantly shorter than those in the general referral group (96 min vs 308 min, 110 min vs 300 min, 122 min vs 286 min, Z=-11.38, -9.27, -7.63, all P<0.01); the overall satisfaction scores in subjects with ultrasound examination, radiology, clinical laboratory and blood pressure abnormities in the intelligent referral group were all higher than those in the general referral group (9.69±0.60 vs 8.36±1.21, 9.09±0.62 vs 8.26±1.27, 9.74±0.69 vs 8.25±1.31; 9.68±0.59 vs 8.34±1.35, respectively; t=-18.47, -18.52, -14.42, -11.77, all P<0.01). Conclusions:The application of intelligent referral mode can improve the visiting rate and hospitalization rate of examinees with major positive results of physical examination, shorten their visiting time, and thus improve their satisfaction.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

OBJECTIVE: To analyze the genetic etiology of a Chinese pedigree affected with short stature. METHODS: A child with familial short stature (FSS) who had presented at the Ningbo Women and Children's Hospital in July 2020 and his parents and paternal and maternal grandparents were selected as the study subject. Clinical data of the pedigree was collected, and the proband was subjected to routine growth and development assessment. Peripheral blood samples were collected. The proband was subjected to whole exome sequencing (WES), and the proband, his parents and grandparents were subjected to chromosomal microarray analysis (CMA). RESULTS: The height of the proband and his father was 87.7cm (-3 s) and 152 cm (-3.39 s) respectively. Both of them were found to harbor a 15q25.3-q26.1 microdeletion, which has encompassed the whole of the ACAN gene which is closely associated with short stature. The CMA results of his mother and grandparents were all negative, and above deletion has not been included in population database and related literature, and was rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). After 14 months of rhGH treatment, the height of the proband has increased to 98.5 cm (-2.07 s). CONCLUSION The 15q25.3-q26.1 microdeletion probably underlay the FSS, in this pedigree. Short-term rhGH treatment can effectively improve the height of the affected individuals.
Child ; Female ; Humans ; Male ; Aggrecans/genetics* ; Dwarfism/genetics* ; East Asian People ; Mutation ; Pedigree

Objective:To explore the correlation between lean nonalcoholic fatty liver disease (NAFLD) and metabolic indicators in a young and middle-aged population undergoing physical examination.Methods:It was a cross-sectional study. A total of 8 250 individuals who underwent routine physical examinations at the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University from January to December 2021 and met the inclusion and exclusion criteria were selected as the research subbjects. The general examination, fasting blood glucose, blood lipids, liver function, renal function, and fasting color ultrasound examination results were analyzed retrospectively to assess the correlation between lean NAFLD and major metabolic indicators using independent sample t-test, chi-square test, and multivariable logistic regression. Results:The prevalence of lean NAFLD was higher in men than in women (50.7% vs. 49.3%, χ2=97.261, P<0.001). After stratifying the age of onset of lean NAFLD, the peak age of onset was found to be between 45 and 59 years, with the prevalence gradually increasing with age. When stratified by body mass index (BMI), the peak incidence of lean NAFLD was observed in individuals with a BMI of ≥20 and <23 kg/m 2, with the prevalence showing a significant upward trend as BMI increased. The systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and serum uric acid in lean NAFLD groupwere all significantly higher than those in lean non-NAFLD group (all P<0.01), and the level of high density lipoprotein was significantly lower than that of lean non-NAFLD group ( t=23.755, P<0.001). The logistic analysis showed that systolic blood pressure ( OR=1.258, 95% CI: 1.081-1.465), diastolic blood pressure ( OR=1.282, 95% CI: 1.056-1.557), total cholesterol ( OR=1.712, 95% CI: 1.525-1.923), triglyceride ( OR=4.115, 95% CI: 3.621-4.676), alanine aminotransferase ( OR=1.467, 95% CI: 1.104-1.950), γ-glutamyltransferase ( OR=1.482, 95% CI: 1.242-1.769), fasting blood glucose ( OR=2.479, 95% CI: 2.092-2.939) and serum uric acid ( OR=1.390, 95% CI: 1.236-1.563) were independent metabolic risk factors for lean NAFLD (all P<0.05). Conclusions:The levels of various metabolic markers in young and middle-aged patients with lean NAFLD increase, and the risk of lean NAFLD increases. Metabolic markers are helpful to screen people at risk of lean NAFLD.

Objective:To investigate the clinical and genetic features of patients with ACTL6B gene variations, and to report novel pathogenic variations of the ACTL6B gene, summarize the clinical phenotypes and genotypes of the gene. Methods:The clinical phenotypes and genotypes of a infant with developmental epileptic encephalopathy carrying the ACTL6B gene variations, who visited the Department of Neurology, Capital Institute of Pediatrics-Peking University Teaching Hospital on March 12, 2021 were analyzed. The phenotypes and genotypes of patients carrying the ACTL6B gene variations reported in the literature were also summarized and analyzed. Results:The proband was a 2-month-old male presented with convulsive seizures, development delay, dystonia, and cherry erythema in the fundus. The whole exome sequencing of his family showed that he carried compound heterozygous variation c.937-2A>G(p.?), c.11delG(p.G4Afs *86) which derived from his parents respectively. These 2 genotypes had not been reported. A total of 42 cases with ACTL6B gene variation were reported in the literature and in this study. There were 11 de novo heterozygous variations and 31 bi-allelic variations inherited from the parents (24 homozygous and 7 compound heterozygous). Individuals with variations tended to have epilepsy, development delay, ambulation disability, speech disability and dystonia. Minor facial dysmorphisms and autism spectrum disorder also can be seen. Conclusion:This paper summarizes the clinical and genetic features of patients with ACTL6B gene variations, reports 2 novel variations and a novel combination of this gene with cherry erythema in the fundus.

ObjectiveTo evaluate the clinical efficacy of TDP （specific electromagnetic wave） combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type. MethodA total of 104 patients with knee osteoarthritis of Qi stagnation and blood stasis type， who received conservative therapy in The Third People's Hospital of Xinjiang Uygur Autonomous Region from July 2019 to December 2021， were randomized into the control group and study group with the random number table method， 52 cases in either group. The control group was treated with TDP， and the study group with TDP and Osteoking. The treatment lasted 1 week for both groups， with 1-month follow-up. Subjective indexes of visual analog scale （VAS） score and Western Ontario McMaster Universities Osteoarthritis Index （WOMAC） score， and objective indexes of visual tenderness index and visual knee range of motion were determined before and after treatment to evaluate the pain and functions of patients. Traditional Chinese medicine （TCM） syndrome score was calculated. The serum erythrocyte sedimentation rate （ESR） and high sensitivity C-reactive protein （hs-CRP） were detected before and after treatment， and the total clinical effective rate was calculated. ResultBefore treatment， the baseline information and all the scores of the two groups were comparable. After treatment， the VAS score， WOMAC score， tenderness index， knee range of motion， and TCM syndrome score were improved in both groups （P<0.01）. After the treatment， the VAS score and WOMAC score of the study group were lower than those of the control group （P<0.01） and the improvement of tenderness index in the study group was better than that in the control group （P<0.05）. The knee range of motion in the study group was better than that in the control group （P=0.061）. The TCM syndrome score of study group was lower than that of control group （P<0.01） after treatment. The post-treatment serum ESR and hs-CRP level in the two groups decreased significantly after treatment， and the study group were lower than those of the control group （P<0.01）. The total clinical effective rate of the study group was 90.4%（47/52）， as compared with the 53.8%（28/52） in the control group （P<0.05）. No obvious adverse events occurred during treatment in both groups. ConclusionThe clinical efficacy of TDP combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type is remarkable， which can improve knee pain and functions， alleviate TCM syndrome， and reduce inflammatory indexes， with high safety.

Objective:To determine the alteration of miRNA profile of human tonsillar epithelial cells induced by enterovirus-A71 (EV-A71) infection.Methods:Human tonsillar epithelial cells UT-SCC-60B were infected with EV-A71 at multiplicities of infection (MOI) of 1 and total RNA was extracted using Trizol reagent. Small RNA library was constructed and high-throughput sequencing was performed using Illumina NextSeq 500. Differential significantly expressed known and novel miRNAs and putative targets were selected after the processing of raw data. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) pathways were analyzed through online database. Kinds of miRNA could target EV-A71 genome was determined through psRNATarget. Validations of random selected miRNAs were done through real-time RT-PCR.Results:A total of 61 known significantly expressed miRNAs (21 miRNAs were down-regulated and 40 miRNAs were up-regulated) and 559 novel significantly expressed miRNAs were identified through high-throughput sequencing. Novel significantly expressed miRNA had typical "hairpin structure" of pre-miRNA. Fold changes of hsa-miR-517b-3p and hsa-miR-199a-5p which was determined by real-time RT-PCR had similar change trends with high-throughput sequencing. Putative targets of significantly expressed miRNA were referred to different biological processes and signaling pathways. A total of 24 significant miRNAs (5 known significantly expressed miRNAs and 19 novel significantly expressed miRNAs) had "seed sequence" in EV-A71 genome.Conclusions:Expression of miRNA profile in UT-SCC-60B was significantly changed by EV-A71 infection and the identified significantly expressed miRNAs potential target EV-A71 genome to regulate EV-A71 replication.

Hand, foot, and mouth disease (HFMD) caused by enterovirus-A71 (EV-A71) has posed heavy disease and economic burdens to young children under 5 years of age and families. Elucidating the pathogenesis of EV-A71 will provide better evidence for prevention and control for EV-A71 infection. miRNAs are a class of non-coding RNA that regulate many biological processes of host cells through manipulating mRNA translation to control the protein levels by direct binding to mRNA, meanwhile, participating the virus-host cell interaction. Here, we mainly review the current knowledge on the biogenesis of miRNA, alterations of miRNA profiles induced by EV-A71, regulation of EV-A71 replication, anti-EV-A71 innate immunity and apoptosis by miRNA direct binding EV-A71 genome or host genes. All these will facilitate understanding the role of miRNA in EV-A71-host cell interaction and pathogenesis of disease caused by EV-A71.