ObjectiveTo investigate the effect of kynurenine-3-monooxygenase （KMO） on the function of fibroblast-like synoviocytes （FLS） in rheumatoid arthritis （RA）. MethodsKMO expression in synovial tissues from RA patients and healthy controls （HC） was analyzed using bioinformatics. Synovial tissues from RA patients and HC were collected， and KMO expression in FLS within synovial tissues was detected by immunofluorescence （IF）. In vitro experiments were performed using human rheumatoid arthritis fibroblast-like synoviocytes （MH7A）. Following KMO overexpression， KMO knockdown， and KMO inhibition with the specific inhibitor Ro61-8048 in MH7A cells， Western blot， CCK-8， EdU， Transwell and ELISA assays were used to evaluate alterations in cell viability， proliferation， migration and secretory function. ResultsBioinformatic analysis revealed significantly higher KMO gene expression in RA synovial tissue compared to the HC group （P<0.001）. IF results showed increased KMO expression in FLS from RA synovial tissues relative to the HC group （P<0.01）. Overexpression of KMO led to enhanced viability， proliferation， migration， and secretory capabilities of MH7A cells （all P<0.05）， whereas knockdown or inhibition of KMO with Ro61-8048 markedly suppressed these functions （all P<0.05）. ConclusionThe expression of KMO is upregulated in the synovial tissues of RA patients and promotes the activation of RA-FLS， suggesting that KMO may serve as a potential therapeutic target for RA treatment.

Objective:To observe the changes of growth parameters and glucose and lipid metabolism indexes in GHD children treated with rhGH for 2 years, and analyze the influence of sex and age on these indexes.Methods:Clinical data of children with 80 cases GHD admitted to the Endocrine and Nutrition Clinic of the Beijing Children's Hospital affiliated to the Capital Medical University from July 2016 to December 2022 were analyzed retrospectively. All patients were treated with rhGH. The growth parameters, growth factors, glucose metabolism and lipid metabolism indexes were collected and calculated before treatment and at 3, 6, 12, 18 and 24 months after treatment, the influence of sex and age on these indexes and the correlations between these indicators and height growth rate were analyzed. Independent-sample t-test was used to compare two groups with normal distribution, one-way ANOVA was used to compare multiple groups, and repeated measures ANOVA was used to compare the mean of each time point within groups. The nonparametric rank sum test was used for the comparison of non-normal distribution measurement data. Pearson correlation analysis was used to analyze the correlation between HGV and each index.Results:A total of 80 children were enrolled, 39 boys and 41 girls. Grouped by age, there were 20 in the 3.00-5.99 age group, 41 in the 6.00-9.99 age group, and 19 in the ≥10.00 age group. All patients after 24 months of treatment had a higher height ((135.13±13.17) cm), HtSDS (-0.73 (-1.04, -0.41)), body weight (29.25 (23.13, 35.00) kg), weight standard deviation score (WtSDS) (-0.44 (-1.03, 0.03)), and body mass index (BMI) (15.99 (14.90,16.92) kg/m 2) compared to before treatment ((115.44±12.87) cm, -2.11 (-2.57, -2.03), 20.00 (16.00,25.00) kg, -1.48 (-2.12, -0.89) and 15.30 (14.45, 16.21) kg/m 2) all increased, and the differences were statistically significant (all P<0.05). The increase in HtSDS in the group aged 3.00-5.99 (1.74±0.29) was higher than that in the group aged 6.00-9.99 (1.57±0.33) and ≥10.00 (1.39±0.45), and the difference was statistically significant ( F=4.84, P=0.010). All patients showed an increase in insulin-like growth factor 1 (IGF-1) (329.50 (268.00, 417.25) μg/L) and insulin-like growth factor binding globulin 3 (IGFBP-3) (6.27 (5.50,6.95) mg/L) after 24 months of treatment compared to before treatment (131.50 (96.48,177.25) μg/L, 4.07 (3.60,4.88) mg/L), with statistical significance (all P<0.05). After treatment for 3 months, 6 months, 12 months, 18 months, and 24 months, children aged ≥ 10.00 years old with IGF-1 (353.00 (221.00, 493.00), (414.84±147.91), 441.00 (287.00, 578.00), (421.68±138.30), 376.00 (290.00, 581.00) μg/L) were higher than these in 3.00-5.99 years old group (181.00 (151.25, 237.75), (216.30±68.48), 239.50 (216.75, 325.00), (284.30±89.12), 293.00 (245.25, 343.75)) μg/L and 6.00-9.99 age group (253.00 (193.50, 345.50), (294.59±90.37), 284.00 (217.50, 377.50), (325.76±90.04), 345.00 (265.00, 431.00) μg/L, the difference was statistically significant (all P<0.05). At 3 months, 6 months, 12 months, and 18 months of treatment, IGFBP-3 levels were observed in children aged ≥ 10.00 years old (6.15 (5.52, 6.46), (6.56±1.26), (6.78±1.33), (6.78±1.38) mg/L) higher than 3.00-5.99 years old group (4.69 (4.43,5.11), (5.18±0.63), (5.61±0.84), (6.08±1.00) mg/L) and 6.00-9.99 age group (5.51 (4.76, 6.35), (5.61±0.81), (5.72±0.78), (6.03±0.80) mg/L, the difference was statistically significant (all P<0.05). All children with HbA1C (5.40 (5.20, 5.58)%), fasting blood glucose (5.06 (4.76, 5.24) mmol/L), triglycerides (0.67 (0.53, 1.02) mmol/L), TyG index (2.24±0.48), and triglyceride/HDL-C ratio (1.05 (0.73, 1.50)) after 24 months of treatment compared to before treatment (5.10 (5.00, 5.28)%, 4.78 (4.51, 5.09) mmol/L, 0.57 (0.47, 0.72) mmol/L, (1.92±0.36), 0.86 (0.65, 1.08). The level of cholesterol increased, and the total cholesterol (3.74 (3.39, 4.31) mmol/L) decreased compared to before treatment (3.95(3.64, 4.54) mmol/L), with statistical significance (all P<0.05). Female patients had higher levels of triglycerides (0.79 (0.59, 1.09) mmol/L) and TyG index (2.31±0.49) than male patients (0.66 (0.53,0.89) mmol/L, (2.16±0.46)) after 18 months of treatment. The triglyceride/HDL-C at 12 months (1.10(0.67, 1.93)), 18 months (1.16(0.83, 1.68)), and 24 months (1.26 (0.79, 1.81)) of treatment ratio was also higher than male patients (0.76 (0.61, 1.09), 0.90 (0.72, 1.08), 0.98 (0.66, 1.30)). Female HDL-C levels at 18 months (1.52 (1.29,1.75) mmol/L) and 24 months (1.45(1.29,1.76) mmol/L) of treatment were significantly lower in males (1.72 (1.45, 1.84), 1.59 (1.43, 1.92) mmol/L) with statistical significance (all P<0.05). HGV was positively correlated with IGF-1 at 12 months ( r=0.243, P=0.030) , 18 months ( r=0.277, P=0.013) and 24 months ( r=0.289, P=0.009), and it was positively correlated with IGFBP-3 at 18 months ( r=0.242, P=0.030) and 24 months ( r=0.236, P=0.035), but it was negatively correlated with HDL-C at 18 months ( r=-0.331, P=0.003) and 24 months ( r=-0.281, P=0.012). Conclusions:RhGH can obviously improve HtSDS and WtSDS in GHD children. Growth factors, glucose metabolism and lipid metabolism should be monitored during the treatment. Especially for female patients (≥10.00 years old), we should closely monitor the indexes of glucose and lipid metabolism in order to avoid metabolic diseases.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective:To compare the efficacy of transpulmonary pressure (Ptp) and driving pressure (DP) in guiding lung-protective ventilation strategies in patients with acute respiratory distress syndrome (ARDS).Methods:In this randomized controlled trial, 22 ARDS patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, were divided into 2 groups ( n=11 each) using a random number table method: Ptp group and DP group. DP group received a tidal volume of 4-6 ml/kg with a plateau pressure<30 cmH 2O (1 cm H 2O=0.098 kPa) and driving pressure<16 cmH 2O. In Ptp group, the positive end-expiratory pressure (PEEP) and tidal volume were adjusted to maintain end-inspiratory Ptp <25 cmH 2O and end-expiratory Ptp 0-5 cmH 2O based on the setting mentioned in DP group. Oxygenation index, PEEP, plateau pressure, central venous pressure, heart rate, mean arterial pressure, parameters of liver and kidney function, mechanical ventilation duration, and the mortality in the intensive care unit were recorded on admission to the operating room and at 24 and 48 h after treatment. Results:Compared to DP group, significant changes were found in the main effects of oxygenation indices and time effects in Ptp group, and significant changes were found in the main effect of PEEP, with mean arterial pressure increasing ( P<0.05), and no significant differences were observed in the other parameters regarding group effects, time effects, or interactions in PEEP group ( P>0.05). Conclusions:Ptp provides a superior efficacy than DP in guiding lung-protective ventilation strategies for the patients with ARDS.

Objective:To investigate the co-occurrence patterns of psychosocial and behavioral problems among children and to identify associated influencing factors.Methods:A multicenter cross-sectional survey was conducted in 2023. A cluster random sample of 19 176 children aged 6-16 years was recruited from middle-income areas across 10 provincial capitals and municipalities in China. Psychological and behavioral problems, including anxiety, compulsive behavior, social withdrawal, depression, somatic complaints, social problems, schizoid, delinquent behaviors, hyperactivity, sexual issues, and aggression, were assessed using the Achenbach Child Behavior Checklist parent version. Co-occurrence was defined as ≥2 concurrent problems. Children were divided into 4 groups by gender and age: boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years. Those children who had psychosocial and behavioral problems were further categorized into the single-problem group, and the co-occurrence group based on assessment results. High-frequency co-occurrence phenotypes of children′s psychosocial and behavioral problems were identified. Demographic factors, such as parental employment, education, as well as psychosocial factors like parent-child relationship, screen time and outdoor activity, were investigated. χ 2 test was used to analyze differences between groups. Multivariate Logistic regression modeling was conducted to identify potential factors. Results:Among 14 711 children (7 501 boys, 7 210 girls) who provided effective questionnaires, the detection rates of single problem in the boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years groups were 4.9% (171/3 461), 6.2% (193/3 120), 3.9% (158/4 040), and 5.1% (208/4 090), respectively; the detection rates of co-occurrence were 7.6% (262/3 461), 7.7% (241/3 120), 4.9% (199/4 040), and 5.7% (234/4 090), respectively. The overall detection rates of co-occurrence was higher than that of single problem ( χ2=25.47, P<0.001). Among children with co-occurrence, there were varied manifestations: in the boys aged 6-11 years group, the detection rates of social withdrawal (69.8% (183/262)), schizoid-like behavior (68.3% (179/262)), and compulsive behavior (67.6% (177/262)) were relatively high; in the girls aged 6-11 years group, the detection rates of schizoid-compulsive behavior (69.3% (167/241)), delinquent behavior (65.6% (158/241)), and hyperactivity (58.9% (142/241)) were relatively high; in the boys aged 12-16 years group, the detection rates of hyperactivity (78.9% (157/199)), compulsive behavior (67.3% (134/199)), and immature behavior (57.3% (114/199)) were relatively high; in the girls aged 12-16 years group, the detection rates of schizoid-like behavior (89.7% (210/234)), immature behavior (59.0% (138/234)), and cruelty (57.7% (135/234)) were relatively high. Maternal bachelor′s degree or higher ( OR=0.78, 95% CI 0.61-0.99, P=0.038) served as co-occurrence protective factors, whereas having 1 or more siblings, increased parent-child conflict and decreased parent-child interaction time ( OR=1.24, 1.41, 1.36; 95% CI 1.02-1.52, 1.15-1.73, 1.02-1.82, all P<0.05) were co-occurrence risk factors. Conclusions:Children exhibit strong co-occurrence tendencies in psychosocial and behavioral problems. Compulsive and schizoid traits are the predominant co-occurring phenotypes for childhood and girls respectively. ?Familial environment plays a critical role, necessitating ?multidimensional clinical assessments and ?family-centered interventions.

Autism spectrum disorder (ASD) is a neurodevelopmental condition originating in early life, presenting significant challenges for affected families and society. ASD is characterized by atypical brain development occurring throughout gestation. Maternal diet during pregnancy plays a crucial role in ASD pathogenesis. Specifically, prenatal multivitamin supplementation and adequate vitamin D intake may reduce ASD risk; similar protective effects have been associated with polyunsaturated fatty acid (PUFA) and iron consumption. Although research findings are inconsistent, prenatal nutritional interventions represent a promising strategy for mitigating the future risk of mental health and other disorders in offspring. Therefore, this article reviews key nutrients implicated in ASD risk during pregnancy, to provide a theoretical foundation for developing precise perinatal nutritional intervention plans.

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Spotted fever group Rickettsia(SFGR)are gram-negative,obligate intracellular pathogens that cause spotted fever rickettsiosis,a zoonotic disease.SFGR invade host cells through the expression of outer membrane proteins and Anaplasma-derived proteins.Then they use virulence factors,including phospholipases and cell surface antigens,to evade or suppress host immune de-fenses,thereby facilitating host colonization and intercellular dissemination,and exerting pathogenic effects.This review summarizes current research progress in various SFGR virulence factors,to further elucidate the pathogenic mechanisms of spotted fever rickettsio-sis,and provide a reference for the prevention and treatment of this disease.

Objective To investigate the effects of three types of twin-block(TB)appliances on the stress and displacement of anterior teeth,periodontal ligaments,and alveolar bone.Methods A three-dimensional(3D)finite element model was constructed,including maxillofacial bones,articular discs,teeth,and periodontal ligaments.Three types of twin-block appliances were designed:classic twin-block(classic-TB),twin-block with acrylic capping(capping-TB),and clear twin-block aligner(CTBA).All appliances had an inclination angle of 70°,and a masticatory force of 200 N was applied to their inclined planes.The finite element method was used to analyze the stress distribution and displacement differences of anterior teeth.Results All three types of TB appliances induced lingual tilting of maxillary anterior teeth and labial tilting of mandibular anterior teeth.The CTBA group showed the greatest lingual displacement and stress of maxillary anterior teeth,with a maximum stress of 30.6 MPa,while the mandibular anterior teeth in this group exhibited the smallest labial displacement(approximately 0.02 mm)and stress.Additionally,the CTBA group had the lowest compressive stress in mandibular anterior teeth,periodontal ligaments,and alveolar bone,whereas the classic-TB group had the highest.Conclusions In the treatment of Angle Class Ⅱ malocclusion,classic-TB(with or without acrylic capping)causes labial inclination of mandibular anterior teeth.Compared with classic-TB,CTBA effectively reduces the compressive stress and displacement of mandibular anterior teeth,potentially minimizing adverse periodontal risks.However,attention should be paid to the lingual displacement of maxillary anterior teeth.