Objective: This study aims to explore the influencing factors, formation mechanisms, and treatment methods of labial protuberance in the anterior maxilla during orthodontic treatment, providing a reference for clinical practice. Method: This study reports a case where the absence of upper anterior teeth 11 and 21, and the retraction tilting movement of teeth 12 and 22, resulted in labial protuberance and gingival hyperplasia. Alveolar osteoplasty and gingivoplasty were performed. The specific changes in the alveolar bone during the retraction of the anterior teeth and the characteristics of its remodeling were analyzed. Combined with relevant literature, the factors influencing the formation of labial protuberance in orthodontic patients, mechanisms, and methods for prevention and treatment were summarized. Results: After periodental surgery follow-up for 6 months, the gingival color and shape of teeth 12 and 22 were good, the labial alveolar bone was normal, and the overall condition was stable. A review of the literature showed that labial protuberance is more common in adult orthodontic patients, and the distance (>4 mm) and speed of retraction of anterior teeth are related to its formation, with the main mechanism likely being differential remodeling of the alveolar bone. In adult patients, the number of active osteoblasts and osteoclasts in the alveolar bone decreases, along with a reduction in metabolic activity and overall cellular activity, which diminishes the reactivity of the alveolar bone. After treatment of anterior teeth retraction, there is insufficient labial bone resorption. Moreover, the lack of mechanical stress-mediated periodontal ligament in the interdental space leads to reduced bone remodeling stimulation in this area, resulting in thickening of the labial alveolar bone of the upper anterior teeth. The remodeling rates of cortical and trabecular bone differ, with active trabecular bone proliferation near the tooth root surface and slow cortical bone resorption near the outer surface, which ultimately results in increased bone thickness at the labial cervical region. Specific case analysis indicates that the retraction distance of the upper anterior teeth in this case was about 6 mm. The alveolar bone at the missing sites of teeth 11 and 21, lacking periodontal ligament stimulation, showed less remodeling and absorption, likely appearing as hyperplasia. The prevention of labial bone protrusion mainly involves controlling the speed and distance of retraction of anterior teeth. Smaller labial protuberances generally do not require treatment, but those affecting function and aesthetics can be addressed with periodontal alveolar osteoplasty. Conclusion After the retraction of anterior teeth in orthodontics, a prominent, hard bone protuberance on the labial side can sometimes occur, which may be due to differential remodeling efficiency in different regions of the alveolar bone. For bone protuberance that influences aesthetics or function, periodontal alveolar osteoplasty can be a reliable option.

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Although indigenous malaria has been eliminated in Wuhan since 2013,imported malaria remains a potential threat as an infectious source of local malaria transmission.The epidemiological and clinical characteristics of imported malaria are particularly important in areas where local malaria has been eliminated.This study was aimed at analyzing the epidemiological and clinical characteristics of imported malaria in Wuhan from 2012 to 2019,to provide a basis for further improving the preven-tion and control of imported malaria.Patients in Wuhan diagnosed with imported malaria from January 1,2012,to December 31,2019,were included in this study.A case-control study was con-ducted to analyze the features of patients with severe malaria.Uni-variate and multivariate logistic regression was used to identify risk factors for prolonged hospital length of stay(LOS).Among 229 imported malaria cases,212(92.6％)were in Chinese citizens,and most cases were in men(96.5％).The gender ratio is 28:1,and the age of cases is mainly concertrated between 18 and 50 years old(89.1％).More than 80％of patients were mi-grant workers,and most cases were infections from African countries(92.6％).Plasmodium falciparum(80.8％)was the dominant species.Fifty-three severe malaria cases were identified during the study period.Compared with uncomplicated cases,severe cases tended to occur in patients with no history of malaria(P=0.008),patients infected with Plasmodium falciparum(P=0.009),and patients who were initially misdiagnosed(P＜0.001).The median LOS was 6 days,and the species of infec-tion(Plasmodium falciparum),the use of antimalarial drugs(group B),antipyretic time(longer than 3 days),and the turn-around time of blood smear microscopy(longer than 3 days)were significantly associated with longer LOS(all P＜0.05).Al-though malaria has been eradicated in Wuhan for many years,imported cases continue to pose a threat.Efforts should be made to strengthen malaria knowledge education for outbound personnel.Additionally,medical institutions must enhance diagnosis and treatment capabilities for malaria,and adhere to standardized treatment processes,and the development of drug resistance and occurrence of severe malaria must be prevented.

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.
Humans ; Cell Proliferation ; Central Nervous System Diseases/drug therapy* ; Inflammation ; Protein Serine-Threonine Kinases/physiology*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVE: To explore the pharmacological mechanism of Bushen Huatan (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS). METHODS: The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting. RESULTS: We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS. CONCLUSION The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Polycystic Ovary Syndrome/drug therapy*

The purpose of the present study was to investigate the effect of glutamate scavenger oxaloacetate (OA) combined with CGS21680, an adenosine A2A receptor (A2AR) agonist, on acute traumatic brain injury (TBI), and to elucidate the underlying mechanisms. C57BL/6J mice were subjected to moderate-level TBI by controlled cortical impact, and then were treated with OA, CGS21680, or OA combined with CGS21680 at acute stage of TBI. At 24 h post TBI, neurological severity score, brain water content, glutamate concentration in cerebrospinal fluid (CSF), mRNA and protein levels of IL-1β and TNF-α, mRNA level and activity of glutamate oxaloacetate aminotransferase (GOT), and ATP level of brain tissue were detected. The results showed that neurological deficit, brain water content, glutamate concentration in CSF, and the inflammatory cytokine IL-1β and TNF-α production were exacerbated in CGS21680 treated mice. Administrating OA suppressed the rise of both glutamate concentration in CSF and brain water content, and elevated the ATP level of cerebral tissue. More interestingly, neurological deficit, brain edema, glutamate concentration, IL-1β and TNF-α levels were ameliorated significantly in mice treated with OA combined with CGS21680. The combined treatment exhibited better therapeutic effects than single OA treatment. We also observed that GOT activity was enhanced in single CGS21680 treatment group, and both the GOT mRNA level and GOT activity were up-regulated in early-stage combined treatment group. These results suggest that A2AR can improve the efficiency of GOT and potentiate the ability of OA to metabolize glutamate. This may be the mechanism that A2AR activation in combination group augmented the neuroprotective effect of OA rather than aggravated the brain damages. Taken together, the present study provides a new insight for the clinical treatment of TBI with A2AR agonists and OA.
Adenosine A2 Receptor Agonists/therapeutic use* ; Adenosine Triphosphate ; Animals ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Glutamic Acid ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/therapeutic use* ; Oxaloacetic Acid/therapeutic use* ; RNA, Messenger ; Receptor, Adenosine A2A/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Water