ObjectiveTo investigate the effects of ethoxysanguinarine （ETH） on angiotensin Ⅱ （Ang Ⅱ）-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 （IRE1）/regulated IRE1-dependent decay （RIDD） signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation， which was identified as a cardiomyocyte apoptosis model. Subsequently， the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 （CCK-8） to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group， a model group （Ang Ⅱ， 1 mmol·L^-1）， and low-， medium-， and high-dose ETH groups （1.25， 2.5， and 5 mmol·L^-1）. Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling （TUNEL） staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins， endoplasmic reticulum stress， and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip， p-IRE1， and Bid in H9c2 cells （P<0.05， P<0.01）， indicating the induction of endoplasmic reticulum stress， activation of the IRE1/RIDD signaling pathway， and initiation of the apoptosis process. Compared with the blank group， the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes， as well as in both early and late apoptosis rates （P<0.01）. The expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 proteins were significantly increased， while the expression level of Bcl-2 protein was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group （P<0.05）. The expression levels of Bid， Bax， and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group （P<0.05， P<0.01）. The high-dose ETH group significantly reduced the expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and significantly increased the expression level of Bcl-2 （P<0.05）. The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins in the high-dose ETH group were significantly decreased （P<0.05， P<0.01）. ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.

ObjectiveTo investigate the effects of ethoxysanguinarine （ETH） on angiotensin Ⅱ （Ang Ⅱ）-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 （IRE1）/regulated IRE1-dependent decay （RIDD） signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation， which was identified as a cardiomyocyte apoptosis model. Subsequently， the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 （CCK-8） to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group， a model group （Ang Ⅱ， 1 mmol·L^-1）， and low-， medium-， and high-dose ETH groups （1.25， 2.5， and 5 mmol·L^-1）. Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling （TUNEL） staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins， endoplasmic reticulum stress， and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip， p-IRE1， and Bid in H9c2 cells （P<0.05， P<0.01）， indicating the induction of endoplasmic reticulum stress， activation of the IRE1/RIDD signaling pathway， and initiation of the apoptosis process. Compared with the blank group， the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes， as well as in both early and late apoptosis rates （P<0.01）. The expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 proteins were significantly increased， while the expression level of Bcl-2 protein was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group （P<0.05）. The expression levels of Bid， Bax， and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group （P<0.05， P<0.01）. The high-dose ETH group significantly reduced the expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and significantly increased the expression level of Bcl-2 （P<0.05）. The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins in the high-dose ETH group were significantly decreased （P<0.05， P<0.01）. ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

BACKGROUND:The Twin-block orthodontic appliance is commonly used for the correction of Class Ⅱ malocclusion.Its mechanism of action in stimulating mandibular growth has been confirmed in many studies,but its impact on maxillary growth is not very clear. OBJECTIVE:By establishing a finite element model to analyze the stress distribution of the maxillary complex,surrounding bone sutures,and maxillary dentition in patients with Class Ⅱ malocclusion wearing Twin-block orthodontic appliances. METHODS:One patient with Class Ⅱ malocclusion who underwent orthodontic treatment at Qingdao Hospital/Qingdao Municipal Hospital of Shandong Rehabilitation University was selected.The bite force data of the patient when wearing the Twin-block orthodontic appliance was measured,and CBCT data were collected.A finite element model was established,including the maxillary complex,peripheral sutures,Twin-block orthodontic appliance,and maxillary dentition.ABAQUS software was used to simulate the stress distribution in the maxilla and maxillary dentition when the patient was wearing the Twin-block appliance. RESULTS AND CONCLUSION:The equivalent stress on the maxillary anterior teeth was significantly smaller than that on the posterior teeth,and the maximum equivalent stress on both sides of the teeth were 4.797 5 Mpa and 8.716 1 Mpa,respectively,which were located at the first premolar.The maximum displacements were presented at the maxillary incisors on both sides of the teeth,which were 0.080 5 mm and 0.081 0 mm,respectively.The maximum equivalent stress on the bone suture was 1.284 Mpa,which was mainly concentrated in the pterygopalatine suture and the frontal-maxillary suture on both sides,and there was almost no difference in the force of the rest of bone sutures;the maximum displacement of the bone suture was 0.07 mm,with the pterygopalatine suture having the largest displacement,followed by the frontal-maxillary suture.The maximal equivalent stress on the maxillary complex was 27.18 Mpa,which was mainly concentrated on both sides of the anterior pyriform foramen of the maxilla,around the nasofrontal suture and around the pterygopalatine suture at the posterior part of the jaws.The maximal displacement of the maxilla was 0.07 mm,which was mainly concentrated on the maxillary alveolar bone.All these findings show that the occlusal force acts on the maxillary complex through the Twin-block appliance,resulting in clockwise rotation of the maxilla and steepening of the dentition plane.Measures should be taken to compensate for this tendency,for example,by considering maxillary molar elongation and intrusion in the process of occlusion,which are not only able to flatten the occlusal plane,but facilitate the mandibular protraction,thereby further improving Class Ⅱ malocclusion orthodontic treatment.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

OBJECTIVE: To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications. METHODS: By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes. RESULTS: The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway. CONCLUSION LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans ; Mouth Neoplasms/metabolism* ; Prognosis ; Carcinoma, Squamous Cell/metabolism* ; Biomarkers, Tumor/metabolism* ; LIM Domain Proteins/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Male ; Female

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.