Objective: To investigate the relationship between serum alanine transaminase (ALT) and carotid intima media thickness (cIMT) in adolescents, providing evidence for early prevention and control strategies for cardiovascular structural abnormalities in adolescents. Methods: Data were obtained from the third follow up survey (from October to November 2023) of the "Huantai Children Cardiovascular Health Cohort", including 1 153 healthy adolescents with complete information. Analysis of variance (ANOVA) was used to compare cIMT across different ALT level groups, and multiple linear regression was employed to analyze the relationship between serum ALT levels and cIMT. Results: Significant differences in cIMT were observed among Q 1, Q 2, and Q 3 ALT level groups [(0.56±0.04) (0.57±0.04) (0.59±0.04)mm, respectively; F=3.61, P <0.01]. After adjusting for covariates, multiple linear regression revealed a positive correlation between ALT levels and cIMT ( β=0.18, P <0.01). Gender subgroup analysis showed similar results in males ( β=0.19, P <0.01), but no statistically significant association was found in females ( β=0.07, P = 0.54). Conclusions Elevated serum ALT levels are associated with an increased risk of vascular structural damage in adolescents, especially in boys. Early detection and control of abnormal serum ALT levels can help to reduce early vascular structural damage and further reduce the risk of adverse cardiovascular events.

Objective: To analyze the trends, gender, and age differences in the incidence of lip and oral cavity cancer in Chinese population from 1990 to 2021 and predict future incidence trends, providing a scientific basis for disease prevention and public health policy. Methods: Incidence data of lip and oral cavity cancer in Chinese population from the Global Burden of Disease (GBD) database from 1990 to 2021 were analyzed. The Joinpoint regression model was used to assess temporal trends, the age-period-cohort model was used to evaluate the independent effects of age, period, and cohort, and the Bayesian age-period-cohort model (BAPC) model was used to predict incidence trends from 2022 to 2044. Results: From 1990 to 2021, the age-standardized incidence rate of lip and oral cavity cancer in Chinese population increased from 2.39/100 000 to 3.76/100 000, and the crude incidence rate rose from 1.71/100 000 to 4.85/100 000. The incidence rate in males was higher and increased more rapidly than in females. Higher incidence rates were prevalent among older populations, a rapid increase in incidence rates occurred during 2003 to 2012, and earlier birth cohorts showed overall higher risks. BAPC predictions indicated a continued rise in incidence from 2022 to 2044. During this period, male incidence stabilized while female incidence increased at a relatively faster rate. Conclusion The incidence of lip and oral cavity cancer in Chinese population has revealed a continuous upward trend, particularly among males and older populations. Future prevention strategies should focus on these high-risk populations.

Objective: To investigate the association of serum alanine aminotransferase (ALT) with left ventricular hypertrophy (LVH) in adolescents, and to provide scientific evidence for the early screening and intervention strategy of cardiac structure damage. Methods: Data were obtained from the third follow up survey (October 2023) of the "Huantai Childhood Cardiovascular Health Cohort Study", including 1 156 healthy adolescents aged 12-17 with complete information. The sample population was stratified into low ( Q 1 group), medium ( Q 2 group), and high ( Q 3 group) ALT levels based on tertiles within the same gender and age groups. Inter group comparisons were conducted using analysis of variance and trend test. A multivariate Logistic regression model was used to analyze the association between ALT levels and LVH, and stratified analyses were performed by gender and age groups. Results: With the increase of ALT quantile level, the detection rate of LVH showed an increasing trend ( Q 1: 3.7%; Q 2: 10.6%; Q 3: 16.7%, Z= 5.89 , P <0.01). After adjusting for potential covariates, compared with the ALT group ( Q 1), the group ( Q 3) increased the risk of developing LVH in adolescents ( OR=2.09, 95%CI =1.21-4.12). Stratified analyses by age and sex showed a significant association only in boys and younger individuals aged 12 to 14 years [ OR (95% CI ) were 2.64(1.04-7.67) and 3.24( 1.35 -9.06), both P <0.05)]. Conclusion Elevated serum ALT levels are associated with an increased risk of LVH in adolescents, and early detection and control of abnormal liver enzyme levels can help reduce early vascular structural damage and prevent adverse cardiovascular events.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

Objective To explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Objective To elucidate the role of let-7 in the pathogenesis of oral squamous cell carcinoma(OSCC)and its underlying molecular mechanism.Methods The expression of let-7 in human oral keratinocyte(HOK),OSCC tissues,and OSCC cells(CAL-27,SCC-25,and SCC-9)was detected by quantitative real-time PCR.Colony formation,scratch,Transwell,and flow cytometry assays were used to examine the effects of let-7 on the proliferation,migration,invasion,and apoptosis of SCC-25 cells.Western blotting was used to detect the expression of Wnt and β-catenin proteins.The correlation between let-7 expression and the clinicopathological cha-racteristics and prognosis of OSCC patients was analyzed.Results let-7 was downregulated in OSCC tissues and cells.let-7 over-expression effectively inhibited the proliferation,migration,and invasion of SCC-25 cells while promoting apoptosis by suppressing acti-vation of the Wnt/β-catenin pathway.let-7 expression was closely associated with tumor stage,lymph node metastasis,and patient survival status.Patients with low let-7 expression exhibited lower overall survival rate.Conclusion let-7 targets and regulates the Wnt/β-catenin pathway,thereby inhibiting proliferation,migration,and invasion of OSCC cells while promoting apoptosis.

Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.

Objective To screen the differential expression profile of circ_RNA in OSCC and to elucidate the molecular mechanism of circ_PVT1 on OSCC carcinogenesis.Methods The transcripts of 3 cases of OSCC and normal tissues were sequenced by high-throughput sequencing using circ_RNA expression profile chip,and the differential gene expression profiles were screened,and GO and KEGG enrichment analysis were performed.The expression level of PVT1 in OSCC tissues,human normal oral mucosal cells and OSCC cells was detected by qRT-PCR.The effect of PVT1 on the biological behavior of SCC-25 and SCC-9 cells was evaluated by MTT exper-iment,Transwell experiment and flow cytometry.The effect of PVT1 on the expression of key proteins in the Wnt3a/β-catenin pathway was evaluated by Western blot.The relationship between the expression of PVT1 and clinical pathological characteristics and prognosis of patients was further studied.Results A total of 403 differentially expressed circ_RNAs were screened by the chip,and the differen-tially expressed genes were enriched in pathways related to cancer progression.PVT1 was highly expressed in OSCC tissues and cells.Silencing PVT1 expression could inhibit the activation of the Wnt3a/β-catenin pathway,thereby effectively inhibiting the proliferation,migration,invasion and cell cycle of SCC-25 and SCC-9 cells and promoting apoptosis.PVT1 expression was only associated with lymph node metastasis and distant metastasis in patients,and those with high expression had a shorter PFS.Conclusion PVT1 promotes the progression of OSCC by regulating the activation of Wnt3a/β-catenin pathway.The research results provide new ideas for the diagnosis and treatment of OSCC.

Objective To elucidate the role of let-7 in the pathogenesis of oral squamous cell carcinoma(OSCC)and its underlying molecular mechanism.Methods The expression of let-7 in human oral keratinocyte(HOK),OSCC tissues,and OSCC cells(CAL-27,SCC-25,and SCC-9)was detected by quantitative real-time PCR.Colony formation,scratch,Transwell,and flow cytometry assays were used to examine the effects of let-7 on the proliferation,migration,invasion,and apoptosis of SCC-25 cells.Western blotting was used to detect the expression of Wnt and β-catenin proteins.The correlation between let-7 expression and the clinicopathological cha-racteristics and prognosis of OSCC patients was analyzed.Results let-7 was downregulated in OSCC tissues and cells.let-7 over-expression effectively inhibited the proliferation,migration,and invasion of SCC-25 cells while promoting apoptosis by suppressing acti-vation of the Wnt/β-catenin pathway.let-7 expression was closely associated with tumor stage,lymph node metastasis,and patient survival status.Patients with low let-7 expression exhibited lower overall survival rate.Conclusion let-7 targets and regulates the Wnt/β-catenin pathway,thereby inhibiting proliferation,migration,and invasion of OSCC cells while promoting apoptosis.