Endodontic microsurgery (EMS) is an oral surgical procedure that utilizes the magnification and illumination provided by a microscope. Fine instruments are used to remove periapical diseased tissues, resect the root apex, and tightly seal the root canal system, aiming to promote the healing of periapical tissues and retain the affected tooth whenever possible. Precise localization and resection of the root apex have always been challenging in EMS. The application of digital technology in EMS can address many issues in traditional endodontic microsurgery. Digital technology offers advantages such as optimizing surgical planning, providing precise positioning guidance, and enhancing operational accuracy. Currently, the commonly used digital technologies in EMS include static and dynamic navigation technologies and oral surgical robots. Static navigation technology enhances surgical predictability through precise preoperative planning and guided fabrication, yet is constrained by its inability to adjust during surgery. Dynamic navigation technology excels in real-time tracking and intraoperative flexibility but demands high hand-eye coordination from surgeons and may be hindered by bulky handheld devices. Oral surgical robots reduce hand tremors and human error in surgery with their high precision, stability, and ability to adjust in real time, but their clinical applicability is limited and their cost is high. In clinical practice, tailored combinations of these technologies can be applied based on case complexity. For simple cases with well-defined anatomy, static navigation alone may suffice. For complex anatomical cases, static navigation can provide initial planning, supplemented by dynamic navigation for real-time guidance or robotic systems for high-precision execution. This paper discusses the workflow, clinical application status and advantages and limitations of these three digital technologies in EMS. The continuous development of digital technology is expected to simplify the operation process, improve the navigation accuracy, and reduce the operation cost. It is believed that with continuous improvement and optimization, these technologies will effectively break through the current bottleneck of the cost of equipment, operation complexity, and accuracy enhancement. These technologies are also expected to further expand the application boundaries, providing more minimally invasive, precise, and time-saving personalized treatment solutions for endodontic diseases.

Cleft lip and palate (CLP) are common congenital craniofacial developmental disorders with a high incidence rate among newborns. Due to the influence of the cleft, an increased frequency of anomalies occurs in cleft-adjacent teeth. This review summarizes the abnormality of tooth development and malposition characteristics of the central incisors, lateral incisors, and canines adjacent to the alveolar cleft in CLP patients and treatment progress in order to provide information for related clinical treatment and research. The literature reveals that central incisors, lateral incisors, and canines adjacent to the alveolar cleft exhibit various types and degrees of abnormalities. The alveolar cleft-adjacent central incisors show significantly smaller mesiodistal diameters, root lengths, and root volumes compared to the non-alveolar cleft side, while the crown-to-root ratio is larger. Further, they are inclined distally and lingually compared to the non-alveolar cleft side. The alveolar cleft-adjacent lateral incisor is the most common missing or impacted tooth and is often affected by microdontia. The total length and root length of the alveolar cleft-adjacent canines are significantly smaller, while the crown-to-root ratio is larger on the alveolar cleft side. In addition, they are inclined mesially and buccally compared to the non-alveolar cleft side. Further, they are higher positioned and located closer to the midline. For developmental anomalies, impacted central incisors can be addressed by orthodontic space preparation to facilitate eruption or surgical crown exposure and orthodontic traction. Treatment of missing lateral incisors can involve orthodontic closure of the gap or preservation of the space for subsequent prosthetic restoration. When lateral incisors present with developmental defects, such as microdontia, peg-shaped teeth, or invaginated teeth, a comprehensive decision is necessary to determine whether to retain and restore or extract the malformed lateral incisors. Treatment of impacted canines after bone grafting involves either extraction or traction to facilitate the eruption of the impacted tooth. For malposition, presurgical orthodontic treatment can correct teeth with excessive inclination or rotation on the cleft side to improve the effectiveness of bone grafting surgery. Postsurgical orthodontic treatment can enhance the stability of bone grafting surgery. Although numerous studies have explored the dental characteristics of patients with CLP, the lack of applicability and specificity still need to be elucidated, thus indicating the need for further research.

Objective: To explore the long term trend of forced vital capacity to weight index (FWI) among Chinese Han students aged 7-18 from 2000 to 2019, and to predict its changes over the next decade, so as to provide scientific evidences for targeted health interventions and school health policies. Methods: Based on the data of the five Chinese National Surveys on Students Constitution and Health conducted from 2000 to 2019, a total of 216 500, 233 565, 215 267, 214 256 and 212 632 Han students aged 7-18 were included, respectively. The long term trend of FWI among students was analyzed, and the GM (1,1) grey model was used to predict FWI changes over the next decade. Subgroup analyses were conducted by sex, age, and urban-rural residence. Results: The FWI levels of Chinese Han students aged 7-18 were (55.30±11.47)(47.43±11.92)(48.11±12.46)(48.75±12.81)(50.93±13.11)mL/kg in 2000, 2005, 2010, 2014, and 2019, respectively. The FWI of Chinese Han students showed a decreasing then increasing trend from 2000 to 2019, reaching the lowest point of approximately 47.03 mL/kg around 2006, and was projected to recover to 52.88 mL/kg by 2029. Boys had higher FWI for each year and the total level than girls from 2000 to 2019( t =72.58-304.66), and the decline between 2000 and 2005 was smaller in boys (13.1%) than in girls (15.4%). However, the gender gap gradually narrowed and was projected to reduce to 5.36 mL/kg by 2029. FWI increased with age, with the largest difference observed in 2014 between the 7-9 and 16-18 age groups (8.62 mL/kg). Before 2014, urban boys had slightly lower FWI than rural boys; the gap narrowed thereafter, and their FWI levels were expected to become similar by 2029. Urban girls generally had higher FWI than rural girls, and the urban-rural gap showed an increasing trend. By 2029, the largest difference was projected to occur in the 13-15 age group, reaching 7.74 mL/kg. Conclusions The FWI of Chinese Han students showed a trend of initial decline followed by a gradual increase from 2000 to 2019, with notable differences across sex, age, and urban-rural residence. Greater attention should be paid to the respiratory health of rural girls, and effective measures should be taken to reduce urban-rural disparities.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P＜0.001)and LAScd(AUC=0.78,P＜0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.

Objective:To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.Methods:Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children′s Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).Results:A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c. 735T>C, ALPL: c. 1324C>T, NEK9: c. 1973G>A, MAGEL2: c. 2024_2025del, LMBR1: c. 423+ 4914A>C, NEB: c. 21273_21276del, COL1A1: c. 2651G>C and c. 2758G>C, ASPM: c. 2473delinsGA, TBX5: c. 704G>A, DYNC2H1: c. 10893del, and DYNC2I2: c. 1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Conclusion:Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.

Objective:To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling.Methods:One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children′s Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher′s exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children′s Hospital (Ethics No.: QFELL-YJ-2025-85).Results:Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences ( P<0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. Conclusion:CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.