Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

Objective:To evalaute the prevalence and determinants of thyroid nodules in children and adolescents in Jiangsu Province.Methods:This study included in-school students aged 8-17 years and selected through stratified cluster random sampling in Jiangsu. Thyroid nodule was diagnosed when its diameter was ≥3 mm. Random urine samples were collected for the detection of urinary iodine concentration with arsenic-cerium catalytic spectrophotometry. Data were analyzed by using χ2 test and logistic regression model. Results:In the 8 201 children and adolescents selected, the thyroid nodule detection rate was 16.10%. Multivariate logistic regression analysis revealed that, compared with those with urinary iodine levels of 100-299 μg/L, boys, those with normal body weight, those who were satisfied with their school performance, urinary iodine concentration ≥300 μg/L ( OR=1.15, 95% CI: 1.01-1.31), being girls ( OR=1.42, 95% CI: 1.26-1.60), being overweight ( OR=1.27, 95% CI: 1.07-1.50), being obese ( OR=1.23, 95% CI: 1.03-1.47), and dissatisfied with school performance ( OR=1.22, 95% CI: 1.04-1.43) were associated with higher likelihood of thyroid nodule detection. Children and adolescents who had solid snacks 2 times per week to 2 times per month ( OR=0.86, 95% CI: 0.74-0.99) or less than 2 times per month ( OR=0.80, 95% CI: 0.68-0.93) were more likely to have lower detection rate compared with those who had solid snacks more than 2 times per week. The detection rate of thyroid nodule increased with age ( OR=1.09, 95% CI: 1.06-1.11). Conclusion:The main factors influencing the detection rate of thyroid nodule in children and adolescents aged 8-17 years in Jiangsu included gender, age, urinary iodine concentration, BMI, self-assessed school performance and dietary habit.

Objective:To identify the risk factors for postoperative adverse ischemic events (IEs) in high-altitude patients requiring intraoperative erythrocyte transfusion.Methods:This was a case-control study. Patient perioperative data and blood transfusion information were obtained through the electronic medical record system, biobank and case follow-up database. Patients with a long history of living at high altitudes who underwent elective tracheal intubation with general anesthesia and received red blood cell transfusion during surgery were selected, and their general characteristics and intraoperative data were collected. Based on the occurrence of ischemic events during postoperative hospitalization, patients were divided into IE group and non-IE group, and the risk factors for IE were identified by multivariate logistic regression analysis (stepwise regression).Results:There were 95 patients in IE group and 232 patients in non-IE group. The results of multivariate logistic regression analysis showed that age ≥65 yr, American Society of Anesthesiologists Physical Status classification Ⅲ, extremely high altitude (≥4 500 m), history of cerebral infarction, high altitude polycythemia, low hemoglobin concentration before blood transfusion, large difference in intraoperative Hb concentrations, massive blood loss and long duration of anesthesia were the risk factors for postoperative IEs in high-altitude patients requiring intraoperative erythrocyte transfusion ( P<0.05). Conclusions:Age≥65 yr, American Society of Anesthesiologists Physical Status classification Ⅲ, extremely high altitude, history of cerebral infarction, high altitude polycythemia, low hemoglobin concentration before blood transfusion, large difference in intraoperative Hb concentrations, massive blood loss and long duration of anesthesia are the risk factors for postoperative IEs in high-altitude patients requiring intraoperative erythrocyte transfusion.

Objective To investigate the efficacy of trastuzumab combined with neratinib on human epidermal growth factor receptor(HER)-2 positive metastatic breast cancer and its impact in the immune function and quality of life of patients.Methods Eighty-two patients with HER-2 positive metastatic breast cancer admitted to our hospital(from June 2022 to December 2023)were included and used as research objects.Patients were separated into the neratinib group and the combination group stochastically,with 41 cases in each group.The neratinib group was treated with neratinib maleate,and the combined group was treated with trastuzumab for injection on the basis of neratinib group for 6 courses of treatment.The clinical efficacy,quality of life scores(FACT-B),immune function indicators(CD4+,CD8+,CD4+/CD8+),tumor marker indicators[carbohydrate antigen(CA)125,CA153,carcinoembryonic antigen(CEA)]and adverse reactions were observed before treatment and after 6 courses of treatment between two groups.Results The overall clinical symptom relief rate was greatly higher in the combination group than that of the neratinib group(P＜0.05).Before treatment,there were no significant differences in quality of life,immune function and tumor markers between the two groups(P＞0.05).After treatment,FACT-B score,CD4+,CD4+/CD8+levels were higher in the two groups than before treatment(P＜0.05),while CD8+,CA125,CA153 and CEA levels were lower than before treatment(P＜0.05),and changes of indexes were more significant in the combination group than those in the nilatinib group(P＜0.05).During treatment,the incidence of adverse reactions was lower in the combination group than that in the nilatinib group(P＜0.05).Conclusion Trastuzumab combined with neratinib is effective and safe in the treatment of HER-2 positive metastatic breast cancer.

Objective:To investigate the effect of riboflavin on cerebral infarction volume and the possible mecha-nism of apoptotic factors with cerebral ischemic injury in mice.Methods:Eighteen C57BL/6J male mice were divided into the sham group,middle cerebral artery occlusion(MCAO)group and riboflavin intervention group(MCAO+RF)randomly.TTC staining was used to observe the infarction of the cerebral tissues;Quantitative real-time PCR(RT-qPCR)was used to detect the mRNA expression of tumor protein p53(p53),cytochrome C(CytC),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteinyl aspartate specific proteinase-3(caspase-3),poly ADP-ribose poly-merase(PARP),cysteinyl aspartate specific proteinase-6(caspase-6)and apoptosis inducing factor(AIF)in different groups,to study the possible mechanism of riboflavin inhibiting neuronal apoptosis.The proteins expression of acetyl-p53(AC-p53),caspase-3 and PARP were analyzed by Western blot.Results:Compared with the MCAO group,the cerebral infarct volume of the MCAO+RF group was obviously reduced(P＜0.01);The relative expression of p53,CytC,caspase-3,PARP,caspase-6 and AIF were significantly lower in the MCAO+RF group(P＜0.05).Addition-ally,significant differences were observed in the proteins expression of AC-p53,caspase-3 and PARP between the MCAO group and MCAO+RF group.Conclusion:Riboflavin has a protective effect against cerebral ischemic injury,which is possibly realized by inhibiting neuronal apoptosis through multiple pathways.

Oral squamous cell carcinoma is a common malignant tumor of the head and neck.Early surgery can achieve good results,but most patients have cervical lymph node metastasis at the time of initial diagnosis.Although surgery combined with radiotherapy or chemotherapy can delay the progression of the disease,the overall prognosis is still not ideal.Especially in patients at stage Ⅲ/Ⅳ,the long-term survival rate has not improved.As a key microbubble in intercellular communication,exosomes contain a large number of biological molecules such as nucleic acids,proteins and lipids.Tumor-derived exosomes play a key role in regulating the tumor micro-environment.This article reviews the effects of tumor-derived exosomes on tumor proliferation,metastasis,immune regulation,diagnosis and treatment in oral squamous cell carcinoma,in order to provide new ideas for early diagnosis and treatment of oral cancer.

Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.