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.

ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.

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*

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

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

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 explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.