ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan（XBS） in normal and chronic bronchitis （CB） mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group， the normal drug administration group， the CB group， the CB drug administration group and the dexamethasone group， with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin （OVA）. The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS（13.2 g·kg^-1） from the 21^st day， and the dexamethasone group mice were simultaneously gavaged with dexamethasone （0.5 mg·kg^-1） until the end of the 35^th day of the experiment. Subsequently， serum samples were collected and evaluated for their efficacy， based on the pharmacological evaluation indicators， to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents， blood-absorbed components， and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently， Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1， CYP3A1， UGT1A1， and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites （including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites） of XBS were unambiguously identified in the serum of normal mice. Additionally， a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites （including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites） of XBS in the serum of CB mice. Among them， 27 prototype components were detected in both states， including 12 flavonoids， 2 alkaloids， 3 triterpenes， 4 organic acids， 3 amides， 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice； however， there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice， the levels of phase Ⅰ metabolites such as oxidation， reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 （P<0.05）， CYP3A1 （P>0.05）， UGT1A1 （P<0.01） and UGT1A6 （P<0.01） enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice， especially in oxidation， reduction， methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1， CYP3A1， UGT1A1 and UGT1A6 in the liver.

OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective To explore the policy foundations of early family education and rehabilitation support systems for children with developmental disabilities aged zero to three years,based on the International Classification of Functioning,Disability and Health(ICF),and to construct a comprehensive,whole-person and whole-lifecycle support system integrating early childhood education and rehabilitation services for families;and to propose corresponding sys-tem architecture,construction pathways and governance models.Methods Policy documents were compared,which were related to children's rehabilitation from the World Health Orga-nization,early education guidelines for children with disabilities from the United Nations Educational,Scientific and Cultural Organization,the U.S.Individuals with Disabilities Education Act,European Union children's reha-bilitation policies,and the"14th Five-Year Plan"from China Disabled Persons'Federation.The related policy frameworks and key content of early family education and rehabilitation were reviewed,and the composition,implementation pathways and governance models of the support system were systymatically analyzed.Results The support system consisted of early screening and assessment,family education and parent training,counsel-ing and personalized education and rehabilitation support,community support and resource integration,and re-mote digital support platforms.The study proposed the implementation pathways for five systems,including early screening and assessment,family education and parent training,counseling and personalized rehabilitation support,community support and resource integration,and remote digital support platforms.It emphasized gover-nance mechanisms such as multidisciplinary collaboration,interdepartmental coordination and support from re-mote digital platforms to build a continuous service chain from standardized assessments to interdepartmental collaboration.Conclusion The person-centered approach and whole life span development concept based on the ICF model,as well as the guiding principles of the health services continuum,provide systematic theoretical and policy support for early childhood education and rehabilitation for children with developmental disabilities aged zero to three years.Through multidisciplinary collaboration,interdepartmental coordination and the application of digital platforms,a scientific,continuous and child-centered support system can be built.This not only facilitates early detection and precise intervention but also promotes multi-party collaboration among families,communities and profes-sional institutions.It will further integrate disability prevention,rehabilitation and healthcare services,thereby im-proving children's functional abilities and family quality of life.

Breast cancer is the most common malignancy among women worldwide and significantly impacts patients'quality of life.With advancements in medical technology,treatment strategies for breast cancer are increasingly shifting toward precision and minimally invasive approaches.High-intensity focused ultrasound(HIFU),characterized by its non-invasive and non-ionizing nature,has been widely applied in the treatment of various benign and malignant tumors.HIFU holds great potential in breast cancer therapy,demonstrating significant antitumor effects in thermal ablation,chemotherapy,immunotherapy,and targeted therapy combinations.HIFU not only ablates tumor tissue and activates antitumor immune responses,but also,when combined with drugs,enhances therapeutic efficacy,promotes drug accumulation in tumor tissues,reduces side effects,and improves long-term outcomes.This article reviews the application of HIFU in the treatment of breast cancer,providing a reference for clinical practice and research.

Objective: To analyze the current status of clinical trial registration for childhood and adolescent obesity, so as to provide insights for the registration and implementation of related trials. Methods: ClinicalTrials.gov and the ChiCTR database were searched for obesity related clinical trial registrations up to 1 June 2025. Data included basic characteristics (registration region, date, funding source, status, sample size), trial design features, participant demographics, interventions, outcome measures, methodology, and reporting quality. Statistical and descriptive analyses were conducted. Results: A total of 1 450 registered studies were included, covering 59 regions globally. North America hosted the highest number of registrations (876, 60.41%), with the United States accounting for the largest share (771, 53.17%). The earliest registered study dated to 1985, while 2016 saw the highest annual registrations ( n =87). Funding sources predominantly originated from universities (834 studies, 57.52%). Currently, completed trials accounted for the majority (1 003 trials, 69.17%). Globally, the majority of studies employed sample sizes within the 11-50 range (331 studies, 22.83%). Interventional studies predominated in design type (1 186, 81.79%), predominantly employing randomized parallel group controlled trials. Main interventions included comprehensive lifestyle interventions, physical activity and exercise interventions, and diet and nutrition interventions. High frequency outcome indicators primarily involved body composition and anthropometric measurements, metabolic and biochemical indicators, etc. Methodology and reporting quality required improvement. Conclusions The registration of clinical trials related to childhood and adolescent obesity globally shows a positive development trend, but issues of regional imbalance and methodological limitations exist. It is necessary to strengthen clinical trial registration norms, optimize study designs, and focus on the innovation of interventions and the systematicity of outcome indicators.

Objective:To investigate the differences and prognostic value of serum myeloid-related proteins 8 and 14 (Mrp 8/14) in patients with acute respiratory distress syndrome (ARDS) induced by pulmonary and extrapulmonary sepsis.Methods:A retrospective cohort study was conducted to collect the general clinical data of septic ARDS patients admitted to the intensive care unit (ICU) of Nanjing Hospital of Nanjing Medical University from August 2021 to February 2024. The serum levels of Mrp 8/14 were detected within 24 hours after admission. According to whether the patients died during ICU stay, the patients with pulmonary ARDS and extrapulmonary ARDS induced by sepsis were divided into survival and death groups, respectively. The differences of Mrp 8/14 and other clinical data between the two groups were compared. Logistic regression analysis was used to analyze the prognostic factors of septic patients with pulmonary ARDS and extrapulmonary ARDS. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum Mrp 8/14 for the prognosis of patients with pulmonary ARDS and extrapulmonary ARDS.Results:A total of 138 patients with sepsis-induced ARDS were enrolled in this study, including 79 patients with pulmonary ARDS and 59 patients with extrapulmonary ARDS. Compared to the death group, the level of serum Mrp 8/14 was significantly lower [Mrp 8/14: 22.90 (17.91, 30.88) μg/mL vs. 10.73 (7.15, 17.20) μg/mL, P<0.05]. Multivariate logistic regression analysis demonstrated that the serum Mrp 8/14 level was an independent risk factor for the prognosis of pulmonary ARDS patients only during the ICU stay ( OR=1.253, 95% CI: 1.110-1.414, P<0.05). ROC curve analysis showed that the area under the curve of serum Mrp 8/14 for the prediction of death in ARDS patients with pulmonary sepsis during ICU stay was 0.855 (95% CI: 0.773-0.938, P<0.05), the cut-off value was 19.230 μg/mL, the sensitivity was 0.718, the specificity was 0.925, and the Yonden index was 0.405. Conclusion:Serum Mrp 8/14 is an effective prognostic indicator for the mortality of ARDS patients with pulmonary sepsis during ICU hospitalization.

Objective By analyzing the levels and distribution characteristics of whole blood metal exposure in four districts and counties in Xinjiang,a population baseline data was established to provide scientific basis for the development of environmental hygiene and health prevention and control intervention measures.Methods Using a stratified random sampling method,252 residents aged 3-80 were selected from four regions in Xinjiang(Altay City,Shuimogou District,Urumqi City,Wuqia County,and Zepu County).1ml of fasting venous blood was collected and the whole blood metal concentration was detected by inductively coupled plasma mass spectrometry(ICP-MS).SPSS21.0statistical software was used to analyze the differences in whole blood metal exposure levels.Results A total of 967 qualified samples were screened.Include metal elements with a detection rate of 75％for lead,manganese,and nickel in whole blood for analysis.Blood lead M(Q1,Q3)is 15.91(11.47,22.41)μg/L;blood manganese M(Q1,Q3)is 10.11(8.29,12.56)μg/L;blood nickel M(Q1,Q3)is 0.90(0.63,1.17)μg/L.There were statistically significant differences in the concentrations of blood lead,blood manganese,and blood nickel in different regions(H were 16.171,27.642,87.690,respectively,P＜0.05).There is a statisti-cally significant difference in blood nickel levels between urban and rural areas(H=19.261,P＜0.05).There were statistically signifi-cant differences in blood lead and blood manganese levels among different ages(H were 31.786,67.631,P＜0.05).There is a statisti-cally significant gender difference in blood lead and blood manganese levels(H were 31.255,19.921,P＜0.05).Conclusion Resi-dents in four districts and counties in Xinjiang have certain levels of internal exposure to lead,manganese,and nickel,and there are re-gional,urban-rural,and population differences.It is suggested that residents in Xinjiang may be at a potential risk of low-level expo-sure to multiple metals in the environment,and further research is needed.