Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

The metabolic activity of adipose tissue,especially the thermogenic function of brown adipose tissue mediated by uncoupling protein 1(UCP-1),plays a significant role in the regulation of energy metabolism and the prevention and treatment of metabolic diseases,cardiovascular diseases and tumors.However,UCP-1 itself could not be directly visualized with existed imaging techniques.The advancements of imaging techniques for indirectly assessing UCP-1 function based on adipose tissue metabolic activity were reviewed in this article.

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

The metabolic activity of adipose tissue,especially the thermogenic function of brown adipose tissue mediated by uncoupling protein 1(UCP-1),plays a significant role in the regulation of energy metabolism and the prevention and treatment of metabolic diseases,cardiovascular diseases and tumors.However,UCP-1 itself could not be directly visualized with existed imaging techniques.The advancements of imaging techniques for indirectly assessing UCP-1 function based on adipose tissue metabolic activity were reviewed in this article.

Carpal tunnel syndrome(CTS)is one of the most common peripheral nerve entrapment disorders,the elevated pressure in the carpal tunnel,high-intensity activities and obesity are the main causes,and the patients with mild to moderate CTS are more prevalent.The main pathogenesis of CTS involves the increasing of carpal tunnel pressure and impaired local blood oxygen supply leading to reduced nerve conduction.Currently,the clinical treatment methods for mild to moderate CTS mainly include surgical and nonsurgical treatments.Nonsurgical treatment is the preferable choice for the patients with mild to moderate CTS.The western medical treatment primarily rely on oral medications,but their long-term use is limited due to the certain adverse effects;the local blockade and extracorporeal shock wave therapies show better efficacy for the patients with frequent activities and severe symptoms;the traditional Chinese medicine treatment also becomes a choice for some CTS patients due to their advantages of less pain,lower medical costs,and significant effectiveness.This study reviews the recent advancements in the pathogenesis and treatment of mild to moderate CTS,in order to design the personalized treatment methods for the mild to moderate CTS patients based on their specific conditions in clinical settings and provide the references for precise treatment of the mild to moderate CTS patients.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Objective:To analyze the current status of lung cancer screening among residents in Urban Beijing Cancer Screening Program, 2014-2019.Methods:Based on an on-going cancer screening program launched by the National Urban Cancer Screening Program, residents aged 40 to 69 were recruited from 80 streets in six districts of Beijing (Dongcheng, Xicheng, Chaoyang, Haidian, Fengtai, and Shijingshan District) by using a cluster sampling method. Subjects who were evaluated as high-risk individuals by using the questionnaire received Low-Dose spiral Computed Tomography (LDCT) screening in designated hospitals. All participants were followed up annually using active and passive follow-up methods to obtain their health outcomes (diagnosed with lung cancer or not). The proportion of high-risk cases evaluated by using the questionnaire, clinical recall rate for receiving LDCT screening, the proportion of cases with positive pulmonary node, incidence rate, cumulative incidence rate, and the proportion of patients with stage 0 or Ⅰ were calculated. Cox proportional hazard regression model was used to estimate the hazard ratio ( HR) and 95% confidence interval (95% CI) among individuals who experienced different screening scenarios. Results:A total of 88 044 residents with the age of (57.4±7.4) with completed high-risk assessment were included in the analysis. 23.14% of participants were evaluated as high-risk individuals by using the questionnaire. The clinical recall rate was 52.26% among the high-risk individuals. The positive rate of pulmonary node detected by LDCT was 10.99%. The incidence rate of lung cancer among males and females aged 40-69 years were 172.82/100 000 person-years and 133.52/100 000 person-years, respectively after 3 years follow-up. The incidence rates increased with age ( P trend<0.001). The incidence rate of lung cancer among high-risk individuals was 259.22/100 000 person-years, with the HR ( 95%CI) about 2.27 (1.83-2.81) when compared with that among low-risk individuals. The incidence rate and cumulative incidence rate of lung cancer among individuals with positive pulmonary node detected by LDCT were 1 825.03/100 000 person-years and 4 615.38/100 000, respectively, with the HR (95% CI) about 13.80 (8.91-21.36) when compared with that among individuals with no or negative pulmonary node. The early diagnosis rate among individuals who received LDCT screening was 70.21%, which was higher than that among individuals with no LDCT screening (45.45%). Conclusion:Individuals with a high risk of lung cancer in Beijing have a better recall rate of receiving LDCT screening. Using LDCT screening among high-risk individuals is an effective strategy to detect lung cancer cases and improve the early detection rates of lung cancer in Beijing, China.

Objective:To analyze the current status of lung cancer screening among residents in Urban Beijing Cancer Screening Program, 2014-2019.Methods:Based on an on-going cancer screening program launched by the National Urban Cancer Screening Program, residents aged 40 to 69 were recruited from 80 streets in six districts of Beijing (Dongcheng, Xicheng, Chaoyang, Haidian, Fengtai, and Shijingshan District) by using a cluster sampling method. Subjects who were evaluated as high-risk individuals by using the questionnaire received Low-Dose spiral Computed Tomography (LDCT) screening in designated hospitals. All participants were followed up annually using active and passive follow-up methods to obtain their health outcomes (diagnosed with lung cancer or not). The proportion of high-risk cases evaluated by using the questionnaire, clinical recall rate for receiving LDCT screening, the proportion of cases with positive pulmonary node, incidence rate, cumulative incidence rate, and the proportion of patients with stage 0 or Ⅰ were calculated. Cox proportional hazard regression model was used to estimate the hazard ratio ( HR) and 95% confidence interval (95% CI) among individuals who experienced different screening scenarios. Results:A total of 88 044 residents with the age of (57.4±7.4) with completed high-risk assessment were included in the analysis. 23.14% of participants were evaluated as high-risk individuals by using the questionnaire. The clinical recall rate was 52.26% among the high-risk individuals. The positive rate of pulmonary node detected by LDCT was 10.99%. The incidence rate of lung cancer among males and females aged 40-69 years were 172.82/100 000 person-years and 133.52/100 000 person-years, respectively after 3 years follow-up. The incidence rates increased with age ( P trend<0.001). The incidence rate of lung cancer among high-risk individuals was 259.22/100 000 person-years, with the HR ( 95%CI) about 2.27 (1.83-2.81) when compared with that among low-risk individuals. The incidence rate and cumulative incidence rate of lung cancer among individuals with positive pulmonary node detected by LDCT were 1 825.03/100 000 person-years and 4 615.38/100 000, respectively, with the HR (95% CI) about 13.80 (8.91-21.36) when compared with that among individuals with no or negative pulmonary node. The early diagnosis rate among individuals who received LDCT screening was 70.21%, which was higher than that among individuals with no LDCT screening (45.45%). Conclusion:Individuals with a high risk of lung cancer in Beijing have a better recall rate of receiving LDCT screening. Using LDCT screening among high-risk individuals is an effective strategy to detect lung cancer cases and improve the early detection rates of lung cancer in Beijing, China.

PURPOSE: This study was designed to assess the protein levels of transformation/transcription domain-associated protein (TRRAP) in invasive ductal breast carcinomas, and investigated the association between TRRAP and the clinicopathological features of breast cancer. METHODS: We examined TRRAP protein expression in 470 breast cancer tissues and normal breast tissues by tissue microarray to study the correlation between TRRAP expression and clinicopathological features. This was analyzed using the chi-square test. Kaplan-Meier survival curves and log-rank tests were applied to analyze the survival status. Cox regression was applied for multivariate analysis of prognosis. RESULTS: The data demonstrated that expression of TRRAP was significantly lower in breast carcinomas (36.6%) than in corresponding normal breast tissues (50.8%). In addition, TRRAP protein levels negatively correlated with tumor size, and indicated poor differentiation, increased nodal involvement, and low p53-positive rates. Analysis of survival revealed that lower TRRAP expression correlated with shorter survival time. Univariate analyses identified TRRAP and progesterone receptor as independent protective factors for breast cancer prognosis. However, Ki-67, tumor size, and nodal involvement appeared to be independent risk factors. CONCLUSION: The findings indicate a significant correlation between TRRAP protein levels and adverse prognosis in breast cancer. Therefore, TRRAP could be a prognostic biomarker for breast cancer. In addition, TRRAP is also a predictive biomarker of breast cancer treatment.
Biomarkers ; Breast Neoplasms* ; Breast* ; Kaplan-Meier Estimate ; Multivariate Analysis ; Prognosis ; Receptors, Progesterone ; Risk Factors

Objective To understand the allocation of radiological diagnostic equipment and the frequency of medical radiation exposure in the medical institutions in Ningxia region,in order to provide the basis for the reasonable application of medical radiation technology.Methods The general survey in the form of the questionnaires was used to investigate and analyze the medical radiation usage of medical X-ray diagnostics,interventional radiology,nuclear medicine and radiotherapy in Ningxia region medical institutions.Results The frequency of X-ray diagnostic radiography in Ningxia region was 727.9 per 1 000 population in 2014.The frequency of X-ray photography examination was the highest,525.2 per 1 000 population,followed bv the frequency of CT scanning,147.9 per 1 000.For others,the frequency was radiotherapy 6.0 per 1 000 population,nuclear medicine 1.8 per 1 000 and interventional radiology 3.8 per 1 000,respectively.These differences were of statistical significance in frequency of X-ray diagnostic examination in five cities' medical institutions in Ningxia (X2 =162 280.7,P ＜ 0.05),also in all medical institutions at different levels (x2 =902 485.2,P ＜ 0.05) and for both frequency of X-ray photography examination and CT scanning in these institutions (x2 =471 574.9,181 887.1,P ＜ 0.05).Conclusions Of the X-ray diagnostic radiography,the CT scanning has becoine a major means next only to the X-ray photography examination.There are differences in frequency of X-ray diagnostic examination in the medical institutions at different levels in different cities of the region.The related regulatory authorities should strengthen the supervision and management of radiation protection in mnedical institutions,to ensure the justification of diagnostic radiology and radiotherapy.