BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

Objective To assess the blood pressure control and its influencing factors among hypertensive patients in communities in different time periods by 24 h ambulatory blood pressure monitoring(24 h ABPM)and provide reference for optimizing the health management services for hypertension in communities. Methods A total of 765 hypertensive patients registered in the hypertension management project of national essential public health services in Sanxiang Town,Zhongshan City from October 2022 to September 2023 were identified as target subjects.The 24 h ABPM devices were distributed for blood pressure monitoring and a questionnaire survey was conducted to analyze the influencing factors of blood pressure control. Results Of all the participants,16.5% did not monitor blood pressure regularly,and 59.2% monitored blood pressure 1-2 times per week.The patients who were not on night shifts/staying up late had higher mean rates of achieving the target blood pressure and the circadian rhythm of blood pressure during 24 h,nighttime,and early morning than those who were on night shifts/staying up late(all P<0.05).The patients who never drank alcohol had higher rate of achieving the target blood pressure in early morning than those who drank alcohol(P=0.012).The average blood pressure during daytime,nighttime,and 24 h were different by sex(all P<0.05).The average blood pressure during nighttime was different by age and job types(all P<0.05).The average blood pressure during daytime,nighttime,and 24 h were different in patients with different body weight types(all P<0.05).The results of the multivariate logistic regression analysis showed that uncontrolled blood pressure during daytime was more likely to occur in male patients(OR=1.394,95%CI=1.045-1.858,P=0.024),and that during nighttime was more likely to be associated with male patients(OR=1.573,95%CI=1.088-2.275,P=0.016)and night shifts(OR=2.467,95%CI=1.198-5.077,P=0.014).It was difficult to achieve blood pressure control in early morning for the patients who drank alcohol for more than three times per week(OR=4.567,95%CI=1.629-12.807,P=0.004),woke up at night(OR=1.800,95%CI=1.125-2.878,P=0.014),and had night shifts(OR=1.579,95%CI=1.102-2.465,P=0.044).The patients on night shifts were more likely to have abnormal circadian rhythm of blood pressure(OR=1.753,95%CI:1.018-3.018,P=0.043). Conclusions The personal characteristics and lifestyle of hypertensive patients significantly affect the blood pressure control in different time periods(daytime,nighttime,and early morning)and the circadian rhythm of blood pressure.The family doctor team of community healthcare institutions can implement targeted and precise intervention measures for hypertensive patients according to the influencing factors of blood pressure control in different time periods,so as to achieve better management effects.
Humans ; Blood Pressure Monitoring, Ambulatory ; Hypertension/physiopathology* ; Male ; Female ; Middle Aged ; Circadian Rhythm ; Blood Pressure ; Surveys and Questionnaires ; Adult ; Aged ; Time Factors

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective:To investigate the perioperative safety, short-term and long-term efficacy, and surgical strategy of laparoscopic partial gastrectomy for gastrointestinal stromal tumors at the esophagogastric junction.Methods:Seventy-eight patients with mesenchymal tumors in the esophagogastric junction were retrospectively enrolled from September 2018 to August 2023 in which the upper edge of the tumor is less than 2 cm from the Z-line or has invaded the Z-line <1/2 circumference. There were 31 males (39.7%) and 47 females (60.3%), with an average age of (57.2±11.8) years and an average body mass index of (24.5±3.5) kg/m 2. All cases were divided into the wedge resection (WR) group ( n=51) and the resection by opening all of the layers of the stomach wall (RASW) group ( n=27) according to the surgical methods. Surgical outcomes, complications, recover and postoperative gastroesophageal reflux of both groups were compared. The measurement data with a normal distribution were represented by mean±standard deviation ( ± s), and values were compared using the independent sample t-test. The measurement data with a skewed distribution were represented by median (interquartile range) [ M( Q1, Q3)], and values were compared using the Mann-Whitney U test. Count data were expressed as examples (percentages) [ n(%)], and the χ2 test was used to compare countable data. A non-parametric test was used to compare the grade data. Results:The WR group had shorter operation time [(97.1±32.6) min vs (149.9±54.9) min, t=-5.33, P<0.001], less intraoperative blood loss [15(10, 20) mL vs 20(10, 50) mL, z=-2.47, P=0.014], shorter postoperative exhaust time [2(1, 3) d vs 3(2, 3) d, z=-2.49, P=0.013], shorter postoperative oral intake time [2(2, 3) d vs 4(2, 5) d, t=-3.70, P<0.001], shorter postoperative semi-liquid diet time[5(4, 6) d vs 7(5, 8) d, z=-3.57, P<0.001], and shorter postoperative hospital stay [5(4, 6) d vs 7(6, 8) d, z=-4.16, P<0.001] than the RASW group, with statistically significant differences. There was no significant difference in short-term (≤30 days) complications between the two groups (2.0% vs 3.7%, z=-0.46, P=0.648). No cases of cardia stenosis occurred in either group. In the WR group, 3 patients developed gastroesophageal reflux at 6 months postoperatively, with 2 patients relieved after taking acid-suppressing drugs and 1 patient not completely relieved. In the RASW group, 1 patient developed gastroesophageal reflux at 6 months postoperatively and was not completely relieved after taking acid-suppressing drugs. No other patients had gastroesophageal reflux. No other patients have gastroesophageal reflux. Conclusions:WR and RASW are safe and feasible for mesenchymal tumors at the esophagogastric junction in which the upper edge of the tumor is less than 2 cm from the Z-line or has invaded the Z-line <1/2 circumference, and has achieved an excellent short-term effect. The choice of surgical approach can be determined based on varions factors such as the location of the tumor, the relationship of the position between the tumor and the cardia, and whether the tumor is exophytic growth.

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

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

INTRODUCTION: Health literacy plays an essential role in one's ability to acquire and understand critical medical information in the coronavirus disease 2019 (COVID-19) infodemic and in other pandemics. We aimed to summarise the assessment, levels and determinants of pandemic-related health literacy and its associated clinical outcomes. METHODS: A systematic review was performed in Medline ® , Embase ® , PsycINFO ® , CINAHL ® and four major preprint servers. Observational and interventional studies that evaluated health literacy related to the novel COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were included. Items used in health literacy instruments were grouped under the themes of knowledge, attitudes and practices. Determinants of health literacy were grouped into five domains: sociodemographic, medical, psychological/psychiatric, health systems-related and others. RESULTS: Of the 2,065 articles screened, 70 articles were included. Of these, 21, 17 and 32 studies evaluated health literacy related to COVID-19, SARS and MERS, respectively. The rates of low pandemic health literacy ranged from 4.3% to 57.9% among medical-related populations and from 4.0% to 82.5% among nonmedical populations. Knowledge about the symptoms and transmission of infection, worry about infection, and practices related to mask usage and hand hygiene were most frequently evaluated. Sociodemographic determinants of health literacy were most frequently studied, among which higher education level, older age and female gender were found to be associated with better health literacy. No studies evaluated the outcomes associated with health literacy. CONCLUSION The level of pandemic-related health literacy is suboptimal. Healthcare administrators need to be aware of health literacy determinants when formulating policies in pandemics.
Humans ; Health Literacy ; COVID-19/epidemiology* ; Severe Acute Respiratory Syndrome/epidemiology* ; Health Knowledge, Attitudes, Practice ; Pandemics ; SARS-CoV-2 ; Coronavirus Infections/epidemiology* ; Middle East Respiratory Syndrome Coronavirus ; Female ; Male