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

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To observe CT and MRI manifestations of gastritis cystica profunda(GCP).Methods Seventeen patients with GCP confirmed by operation or biopsy pathology were enrolled,and lesions'CT and MRI manifestations were observed.Results Among 17 cases,16 cases(16/17,94.12％)were found with single lesion and 1(1/17,5.88％)with diffuse multiple lesions.The lesion located in the fundus of stomach in 5 cases(5/17,29.41％),in the body of stomach in 4 cases(4/17,23.53％),in the cardia and antrum of stomach each in 3 cases(3/17,17.65％)and in the pylorus in 1 case(1/17,5.88％),while 1 case(1/17,5.88％)was found with diffused multiple lesions within stomach.Non-enhance CT showed local thickening of gastric wall in 10 cases(10/17,58.82％),all were isodensities,and the mucosa uniformly enhanced in contrast enhance CT(CECT).Predominately cystic lesion in 5 cases(5/17,29.41％)presented as submucosal cystic protrusions,and grew into the stomach cavity with circular or oblong low density in non-enhanced CT,while sandwich enhancement of mucosa was observed in CECT.Among these 5 cases(5/17,29.41％),MRI showed lesion confined to the submucosa with low signal on T1WI and high signal on T2WI,while diffusion weighted imaging showed unrestricted diffusion,and the enhancement pattern was consistent with that of CT in 2 cases.In other 2 cases(2/17,11.77％)with cystic-solid lesion,non-enhanced CT showed soft tissue density,while CECT showed lump-like stratified enhancement.Conclusion CT and MRI manifestations of GCP had certain characteristics.

Objective By analyzing the gene expression data in TCGA-THCA dataset,the differentially expressed genes related to thyroid carcinoma(THCA)were identified,a risk model was construct,and the role of CCL chemokine family in the development of THCA and its effect on the tumor immune microenvironment were investigated.Methods TCGA-THCA dataset was downloaded and analyzed,including 512 cancer samples and 59 adjacent tissue samples.The differentially expressed genes were obtained by taking the intersection of R packages of differential analysis,and the principal component analysis(PCA),Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed.CellMarker,monocle,and CellChat were used to explore the Cell atlas,pseudotemporal trajectory,and cellular communication.Results A total of 698 up-regulated genes and 285 down-regulated genes were identified.PCA showed that there were significant differences in gene expression patterns between the THCA group and the normal group.GO and KEGG enrichment analysis revealed that differentially expressed genes were mainly involved in biological processes such as extracellular matrix tissue,cell junction assembly,and complement system.The results of risk model showed that the CCL genes was significantly correlated with poor prognosis(P=0.005).Single cell analysis revealed that fibroblasts played a key role in the development of THCA,and the expression of CCL gene was significantly up-regulated in fibroblasts(P<0.05).The results of pseudotemporal trajectory analysis showed that CCL gene was differentially expressed during cellular differentiation;the results of cellular communication analysis showed that the interaction between fibroblasts and endothelial cells is crucial in the tumor microenvironment.Conclusion The expression of CCL chemokine family in THCA is closely related to poor prognosis,especially CCL4,which activates the downstream signaling pathways by interacts with CCR receptors of cancer-associated fibroblasts,thereby promoting the development of cancer.These findings provide novel insights for understanding the role of CCL chemokine family in THCA and its regulation of the tumor immune microenvironment.

Objective:To explore the epidemiological characteristics and risk factors of gastroesophageal reflux disease (GERD) in Rongcheng city.Methods:From June to December 2023, 4 421 permanent residents of Rongcheng city were selected as the survey subjects, and an epidemiological investigation of GERD was conducted through a combination of telephone interviews and medical records review.Results:A total of 4 803 permanent residents of Rongcheng city were investigated in this study, and the loss of follow-up rate was 7.95%(382/4 803). The prevalence rate of GERD was 6.11%(270/4 421). Compared with the non-GERD group, patients in the GERD group were older, had a higher body mass index (BMI), had a higher proportion of males, and had a lower proportion of married patients ( P<0.05). The results of single factor analysis showed that gallbladder polyp, enteritis, Helicobacter pylori infection, colon polyp, peptic ulcer, chronic gastritis, coronary heart disease, hypertension, diabetes, pharyngitis, drinking history, smoking history, sleep problems or troubles, and eating fish, shellfish, shrimp and seaweed were the influencing factors of GERD ( P<0.05). Multiple Logistic regression analysis showed that male, gallbladder polyp, enteritis, Helicobacter pylori infection, chronic gastritis, coronary heart disease, hypertension, diabetes, pharyngitis, and sleep problems or troubles were independent risk factors for GERD ( P<0.05), while married and eating fish, shellfish, shrimp and seaweed were protective factors ( P<0.05). The scores of Health Questionnaire Depression Scale (PHQ-9), Generalized Anxiety Scale (GAD-7) and Health Questionnaire Somatic Symptom Group Scale (PHQ-15) in the GERD group were higher than those in the non-GERD group: 8(5, 12) scores vs. 2(1, 4) scores, 8(5, 11) scores vs. 2(2, 5) scores, 12(8, 16) scores vs. 4(2, 5) scores, there were statistical differences ( P<0.01). The results of Spearman correlation analysis showed that the three mental state scales and GERD scale (GerdQ) scores had positive correlationsrespectively ( r = 0.150, 0.122, 0.153, P<0.05). Conclusions:The etiology and pathogenesis of GERD are related to living habits, basic diseases, mental factors and other factors. In order to reduce the incidence rate of GERD, attention should be paid to the adjustment of personal living habits and eating habits, as well as mental health.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

OBJECTIVES: With the accelerating aging of the population and the rising prevalence of chronic diseases, the number of patients with pressure injuries (PIs) has increased markedly, prolonging the period of disease-related care. Informal caregivers play a critical role in the daily care of patients with pressure injuries, and their care burden has become increasingly prominent. This study aims to investigate the current status and influencing factors of care burden among informal caregivers of patients with PIs, providing evidence for targeted intervention strategies. METHODS: A total of 170 informal caregivers of patients with PIs were selected by convenience sampling from the Third Xiangya Hospital of Central South University. General demographic and clinical data of both patients and caregivers were collected. The Zarit Caregiver Burden Inventory (ZBI), Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, General Self-Efficacy Scale (GSES), and Family Caregiver Task Inventory (FCTI) were used to assess caregiving burden, knowledge-attitude-practice level, self-efficacy, and caregiving ability, respectively. Pearson correlation analysis was conducted to evaluate relationships among ZBI, Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, GSES, and FCTI scores. Stepwise multiple linear regression analysis was used to identify factors influencing caregiving. RESULTS: Among the 170 patients with pressure injuries, the age was (65.52±15.88) years; 118 (69.41%) were male and 52 (30.59%) were female. The duration of PIs was less than 1 month in 108 (63.53%) cases and 1 to 6 months in 40 cases (23.53%). Stage II injuries were predominant (135 cases, 79.41%). A total of 193 pressure injury sites were recorded, most commonly located at the sacrococcygeal region (127 sites, 65.80%), followed by the head (3 sites, 1.55%), shoulder and back (9 sites, 4.66%), feet (24 sites, 12.44%), and other regions (30 sites, 15.55%). Informal caregivers were 48.82% aged 46 to 59 years, 54.71% female, 41.77% primarily spouses and 47.06% children of the patients, and 77.06% lived with the patients. Caregivers who received assistance from others or had higher family per-capita monthly income reported significantly lower caregiver burden scores than those without assistance or with lower income (all P<0.001). The total ZBI score was 50.89±14.95, indicating a moderate burden. The total scores of the Knowledge-Attitude-Practice Scale for Informal Caregivers, GSES, and FCTI were 50.61±7.22, 26.03±7.11, and 14.76±8.70, respectively. Pearson correlation analysis revealed that ZBI scores were correlated with scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs (r=-0.543, P<0.001), GSES scores (r=-0.545, P<0.001), and FCTI scores (r=0.800, P<0.001). The scores on Knowledge-Attitude-Practice Scale for Informal Caregivers of patients with PIs were correlated with GSES scores (r=0.500, P<0.001) and FCTI scores (r=-0.461, P<0.001); GSES scores was negatively correlated with FCTI scores (r=-0.415, P<0.001). Stepwise multiple linear regression analysis showed that assistance availability, family per-capita monthly income, total scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, total GSES score, and total FCTI score were the main influencing factors of caregiver burden, jointly explaining 79.38% of its variance. CONCLUSIONS The main factors influencing the caregiving burden of informal caregivers of patients with PIs include the availability of assistance, family per-capita monthly income, total score on the Knowledge-Attitude-Practice Scale for Informal Caregivers of PI patients, total score on the GSES, and total score on the FCTI. Developing targeted intervention strategies addressing these factors may help alleviate the caregiving burden among informal caregivers of patients with PIs.
Humans ; Caregivers/psychology* ; Pressure Ulcer/nursing* ; Female ; Male ; Middle Aged ; Cost of Illness ; Adult ; Aged ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; Self Efficacy ; Caregiver Burden ; China