High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

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

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

To investigate the clinical utilization of Rituximab biosimilar (Rituximab injection) in order to provide references for evaluating its rationality and economic value in clinical application.

OBJECTIVE To explore the application effects of the multi-disciplinary treatment （MDT）-based continuous pharmaceutical care system in patients undergoing anti-infection treatment. METHODS This research team innovatively developed an MDT continuous pharmaceutical care system， which was applied to cases of anti-infection treatment following MDT due to infection， aiming to innovate the continuous medication supervision model. A retrospective analysis method was used to collect data from 150 patients in the intensive care unit who underwent conventional anti-infection MDT consultations from January to October 2021 in Banan Hospital Affiliated to Chongqing Medical University， serving as the control group， and 130 patients in the intensive care unit who were under the MDT continuous pharmaceutical care system from January to October 2022 were selected as the intervention group. The general information of the patients， the information continuous tracking management， the outcomes of anti- infection treatment， adverse drug reactions， antibacterial drug management indicators， and the degree of satisfaction of relevant medical staff with the clinical pharmacists’ pharmaceutical services were compared between the two groups. RESULTS Comparison of general information between the two groups showed no statistically significant differences （P＞0.05）. The proportion of continuous tracking management in the intervention group was significantly higher than in the control group （P＜0.01）， and the differences in the initiators and reasons for continuous tracking management between the two groups were statistically significant （P＜0.05）. The intervention group had better outcomes in anti-infection treatment compared to the control group （P＜0.05）. The antibacterial drug management indicators （total length of hospital stay， duration of antibacterial drug use， total drug costs， and amount of antibacterial drugs used） in the intervention group were significantly lower than in the control group， while overall degree of satisfaction among medical staff was significantly higher in the intervention group than in the control group （P＜0.05）. No statistically significant differences were found in adverse reaction occurrence and antibacterial drug costs between the two groups （P＞0.05）. CONCLUSIONS The application of this system in patients who underwent anti-infection treatment after MDT can achieve continuous multi-disciplinary tracking management with clinical pharmacists at the core， which is beneficial for promoting the follow-up efficiency of the MDT team， raising the quality of clinical pharmacists’ pharmaceutical services， strengthening treatment outcomes， and promoting the rational use of antibacterial drugs in clinical practice.

[Objective] To analyze the characteristics of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 allele polymorphisms among cord blood donors in Guangdong population. [Methods] According to HLA high resolution genotyping data of 32 717 samples of cord blood donors from Guangdong Cord Blood Bank from January 2009 to December 2023, the allele frequencies were calculated by direct counting and the haplotype frequencies were calculated by using Arlequin software 3.5.2.2. [Results] A total of 102 HLA-A alleles, 160 HLA-B alleles and 96 HLA-DRB1 alleles were detected in 32 717 samples. Among them, 46 HLA-DPB1 alleles were detected in 5 377 samples, and 66 HLA-C alleles and 35 HLA-DQB1 alleles were detected in 13 310 samples. The most common alleles were HLA-A^*11∶01 (28.96%), HLA-B^*40∶01 (15.23%), HLA-DRB1^*09∶01 (15.72%), HLA-C^*01∶02 (19.40%), HLA-DQB1^*03∶01 (20.85%) and HLA-DPB1^*05∶01 (40.79%). The most common 3 loci haplotype and 6 loci haplotype were HLA-A^*02∶07-B^*46∶01-DRB1^*09∶01 (1.55%), HLA-C^*07∶02-DQB1^*03∶01-DPB1^*05∶01 (1.77%), HLA-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (3.31%) and HLA-A^*02∶07-B^*46∶01-C^*01∶02-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (0.30%). [Conclusion] In this study, the allele and haplotype frequencies of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 were obtained in the cord blood donors in Guangdong, which can provide important reference data for HLA gene related research and the selection of donors for clinical application.

The aim of this study was to investigate the effect of amentoflavone(AF)on airway inflammation in asthmatic young rats and its mechanism.The asthmatic model of young SD rats was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).The rats were randomly grouped into asthma model(M)group,dexamethasone(DXMS)group,AF low(AF L),AF medium(AF M),AF high(AF H)dose group and normal control group(CT)group.After administration,the airway reactivity was detected with non-invasive lung function instrument and the inflammatory cell types in bronchoalveolar lavage fluid(BALF)were analyzed and counted by Giemsa staining.Furthermore,hematoxylin-eosin(HE)staining was applied to evaluate the pathological morphology of lung and bronchial tissues,enzyme-linked immunosorbent assay(ELISA)kits were used to detect the content of inflammatory factors in serum,Western blot was applied to detect the protein expression of GMP-AMP synthase(cGAS),interferon gene stimulator(STING),phosphorylated interferon regulatory factor 3(p-IRF3)and interferon regulatory factor 3(IRF3)in lung tissue of rats.Compared with the CT group,the asthma model group showed obvious pathological damage of bronchial tissue and lung tissue,higher level of airway reactivity,higher pathological scores of lung tissue and bronchial tissue,increased total number of inflammatory cells and the number of monocytes,eosinophils,neutrophils and lymphocytes in BALF,higher levels of inflammatory factors in serum,and higher expression levels of cGAS,STING and p-IRF3/IRF3 proteins in lung tissue(P<0.05).Compared with the M group,the pathological damage of lung and bronchus tissue in asthmatic rats was relieved after treatment with DXMS and high-dose AF,the airway reactivity,pathological score of lung tissue and bronchial tissue,total number and classification of inflammatory cells in BALF,inflammatory factors in serum and expression of cGAS,STING,p-IRF3/IRF3 proteins in lung tissue were obviously lower(P<0.05).In conclusion,AF can alleviate airway inflammation in asthmatic young rats,possibly by inhibiting cGAS-STING signal pathway.