Improved Measurement of the Differential Polarizability Using Co-Trapped Ions.

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Application of Mendelian randomization analysis in investigating the genetic background of blood biomarkers for colorectal cancer.

Colorectal cancer (CRC), a malignancy affecting the colon and rectum, ranks as the third most common cancer worldwide and the second leading cause of cancer-related deaths. Early detection of CRC is crucial for preventing metastasis, reducing mortality, improving prognosis, and enhancing patients' quality of life. Genetic factors play a significant role in CRC development, accounting for up to 35% of the disease risk. Genome-wide association studies have identified several genetic loci associated with CRC risk. However, these studies often lack direct evidence of causality. While traditional blood biomarkers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are widely used for CRC diagnosis and monitoring, their sensitivity and accuracy in early diagnosis are limited. Thus, there is a pressing need to develop new biomarkers that reflect the genetic background of CRC to improve early detection and diagnostic accuracy. In addition, understanding the genetic mechanisms underlying these biomarkers is essential for elucidating CRC pathogenesis and developing precise personalized treatment strategies. Mendelian randomization (MR) analysis, as an emerging epidemiological tool, can accurately assess the causal relationship between genetic variations and diseases by reducing confounding biases in observational studies. MR analysis has been applied in evaluating the causal impact of various blood biomarkers on CRC risk, shedding lights on the potential causal relationships between these biomarkers and CRC pathogenesis in the context of genetic background. In this review, we summarize the applications of MR analysis in studies of blood biomarkers for CRC, aiming to enhance the early diagnosis and personalized treatment of CRC.

Spatial distribution of liver cancer incidence in shenqiu county, henan province, china: a spatial analysis.

Liver cancer is a common and leading cause of cancer death in China. We used the cancer registry data collected from 2009 to 2011 to describe the spatial distribution of liver cancer incidence at village level in Shengqiu county, Henan province, China. Spatial autocorrelation analysis was employed to detect significant differences from a random spatial distribution of liver cancer incidence. Spatial scan statistics were used to detect and evaluate the clusters of liver cancer cases. Spatial clusters were mapped using ArcGIS 10.0 software in order to identify their physical location at village level. High cluster areas of liver cancer incidence were observed in 26 villages of 7 towns and low cluster areas were observed in 16 villages of 4 towns. High cluster areas of liver cancer incidence were distributed along the Sha Ying River which is the largest of tributary of the Huai River. Role of water pollution in Shenqiu County where the high cluster was found deserves further investigation.

[Recent advances in treatment of patients with castration-resistant prostate cancer after docetaxel failure].

The standard first-line treatment of castration-resistant prostate cancer (CRPC) is docetaxel-based chemotherapy. However, CRPC may not respond to docetaxel due to drug resistance or other causes. Several new therapeutic agents have been developed, some of which are approved by FDA or on clinical trials. The mechanisms of action of these agents include stabilizing microtubules, inhibiting hormone synthesis, blocking androgen receptor, bone targeting or immune regulation. In this article we review the novel therapeutic options for CPRC after docetaxel failure.

Changes in Notified Incidence of Pulmonary Tuberculosis in China, 2005-2020.

Objective: To evaluate the trend of notified incidence of pulmonary tuberculosis (PTB) in China at different periods by population and region and to explore the effect of TB prevention and control in recent years. Methods: Using pooled data on TB cases reported by the TB Information Management Reporting System (TBIMS) from 2005 to 2020, we calculated the annual percentage change (APC) using the Joinpoint regression model. Results: From 2005 to 2020, a total of 16.2 million cases of PTB were reported in China, with an average notified incidence of 75.5 per 100,000 population. The age standardization rate (ASR) continued to decline from 116.9 (/100,000) in 2005 to 47.6 (/100,000) in 2020, with an average annual decrease of 5.6% [APC = -5.6, 95% confidence interval ( CI): -7.0 to -4.2]. The smallest decline occurred in 2011-2018 (APC = -3.4, 95% CI: -4.6 to -2.3) and the largest decrease in 2018-2020 (APC = -9.2, 95% CI: -16.4 to -1.3). From 2005 to 2020, the ASR in males (159.8 per 100,000 in 2005, 72.0 per 100,000 in 2020) was higher than that in females (62.2 per 100,000 in 2005, 32.3 per 100,000 in 2020), with an average annual decline of 6.0% for male and 4.9% for female. The average notified incidence was the highest among older adults (65 years and over) (182.3/100,000), with an average annual decline of 6.4%; children (0-14 years) were the lowest (4.8/100,000), with an average annual decline of 7.3%, but a significant increase of 3.3% between 2014 and 2020 (APC = 3.3, 95% CI: 1.4 to 5.2); middle-aged (35-64 years) decreased by 5.8%; and youth (15-34 years) decreased by an average annual rate of 4.2%. The average ASR in rural areas (81.3/100,000) is higher than that in urban areas (76.1/100,000). The average annual decline in rural areas was 4.5% and 6.3% in urban areas. South China had the highest average ASR (103.2/100,000), with an average annual decline of 5.9%, while North China had the lowest (56.5/100,000), with an average annual decline of 5.9%. The average ASR in the southwest was 95.3 (/100,000), with the smallest annual decline (APC = -4.5, 95% CI: -5.5 to -3.5); the average ASR in the Northwest China was 100.1 (/100,000), with the largest annual decline (APC = -6.4, 95% CI: -10.0 to -2.7); Central, Northeastern, and Eastern China declined by an average of 5.2%, 6.2%, and 6.1% per year, respectively. Conclusions: From 2005 to 2020, the notified incidence of PTB in China continued to decline, falling by 55%. For high-risk groups such as males, older adults, high-burden areas in South, Southwest, and Northwest China, and rural regions, proactive screening should be strengthened to provide timely and effective anti-TB treatment and patient management services for confirmed cases. There is also a necessity to be vigilant about the upward trend of children in recent years, the specific reasons for which need to be further studied.

Using interrupted time series design to analyze changes in hand, foot, and mouth disease incidence during the declining incidence periods of 2008-2010 in China.

OBJECTIVE: To identify patterns of hand, foot and mouth disease (HFMD) incidence in China during declining incidence periods of 2008, 2009, and 2010. METHODS: Reported HFMD cases over a period of 25 months were extracted from the National Disease Reporting System (NDRS) and analyzed. An interrupted time series (ITS) technique was used to detect changes in HFMD incidence rates in terms of level and slope between declining incidence periods of the three years. RESULTS: Over 3.58 million HFMD cases younger than 5 years were reported to the NDRS between May 1, 2008, and May 31, 2011. Males comprised 63.4% of the cases. ITS analyses demonstrated a significant increase in incidence rate level (P<0.0001) when comparing the current period with the previous period. There were significant changes in declining slopes when comparing 2010 to 2009, and 2010 to 2008 (all P<0.005), but not 2009 to 2008. CONCLUSION: Incremental changes in incidence rate level during the declining incidence periods of 2009 and 2010 can potentially be attributed to a few factors. The more steeply declining slope in 2010 compared with previous years could be ascribed to the implementation of more effective interventions and preventive strategies in 2010. Further investigation is required to examine this possibility.

Influence of Built Environment in Hygienic City in China on Self-rated Health of Residents.

Objective: To assess the subjective perception of residents on the built environment in hygienic cities and its relation to the self-rated health (SRH) status of residents, providing a basis for a better promotion on construction of health-supportive environments. Methods: The online survey was adopted with the respondents recruited from residents living in Chaoyang District of Beijing in January 2021. With SRH level as the dependent variable, two-category logistic regression analysis was conducted to analyze the impact of the built environment in hygienic cities on the SRH status of residents. Results: A total of 1,357 respondents were enrolled in this study. After controlling confounding factors, four aspects in the built environment in hygienic cities were detected remarkable influences on the SRH level of residents, including enough green space in the living area [odds ratio ( OR) = 1.395, 95% confidence interval (95% CI): 1.055-1.845], clean and hygienic living environment ( OR = 1.472, 95% CI: 1.107-1.956), residents' confidence in drinking water safety in the living area ( OR = 1.856, 95% CI: 1.354-2.544) and residents' confidence in food safety in the living area ( OR = 1.405, 95% CI: 1.027-1.921). Conclusion: Regarding city construction, the government should focus more on the subjective perception of residents on built environments to build a supportive environment benefiting the health of residents.

Joint Association of Metabolic Health and Obesity with Ten-Year Risk of Cardiovascular Disease among Chinese Adults.

OBJECTIVE: This study aims to investigate the association of metabolic phenotypes that are jointly determined by body mass index (BMI) or fat mass percentage and metabolic health status with the ten-year risk of cardiovascular disease (CVD) among Chinese adults. METHODS: Data were obtained from a cross-sectional study. BMI and body fat mass percentage (FMP) combined with the metabolic status were used to define metabolic phenotypes. Multiple linear regression and logistic regression were used to examine the effects of metabolic phenotypes on CVD risk. RESULTS: A total of 13,239 adults aged 34-75 years were included in this study. Compared with the metabolically healthy non-obese (MHNO) phenotype, the metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO) phenotypes defined by BMI showed a higher CVD risk [odds ratio, OR (95% confidence interval, CI): 2.34 (1.89-2.89), 3.45 (2.50-4.75), respectively], after adjusting for the covariates. The MUNO and MUO phenotypes defined by FMP showed a higher CVD risk [ OR (95% CI): 2.31 (1.85-2.88), 2.63 (1.98-3.48), respectively] than the MHNO phenotype. The metabolically healthy obese phenotype, regardless of being defined by BMI or FMP, showed no CVD risk compared with the MHNO phenotype. CONCLUSION: General obesity without central obesity does not increase CVD risk in metabolically healthy individuals. FMP might be a more meaningful factor for the evaluation of the association of obesity with CVD risk. Obesity and metabolic status have a synergistic effect on CVD risk.

Age-period-cohort analysis of pulmonary tuberculosis reported incidence, China, 2006-2020.

BACKGROUND: Tuberculosis (TB) poses a severe public health challenge in China and worldwide. This study evaluated the effects of age, period, and birth cohort on reported incidence trends of TB based on population and refined the characteristics of high-risk groups. METHODS: Aggregate data that reported pulmonary tuberculosis (PTB) cases from China Tuberculosis Management Information System (TBIMS) from 2006 to 2020 were used to analyze effect coefficients through the age-period-cohort (APC) model based on intrinsic estimator (IE) method, and converted them into relative risk (RR) to estimate trends. RESULTS: A total of 14.82 million cases of PTB were reported in China from 2006 to 2020, showing a continuous downward trend. The reporting rate increased with age by age group, with 70-74 years old being 2-3 times higher than that in 20-24 years old. APC analysis model showed that age effects were bimodal in 20-24 years old [RR = 2.29, 95% confidence interval (CI): 1.73-3.03] and 70-74 years old (RR = 1.95, 95% CI: 1.67-2.27), and lower than the overall average in the groups under 15 years old. Stratified results showed that the risk was higher for women under age 40 than men and higher for men over 40. The risk was higher in urban than in rural areas under 30 years old and slightly higher in rural than in urban between 30 and 64 years old. The risk for 15-34 years old was significantly higher in the east than in other regions. The period effects showed a decreasing trend, and the risk was higher in rural in recent years. Except for cohorts born in 1961-1965 and 2001-2005, where the RR increased, the later the cohort was born, the lower the risk. The cohort 1926-1930 in eastern had the highest risk (RR = 3.49, 95% CI: 2.44-4.98). CONCLUSIONS: The reported incidence of PTB continued to decline in China from 2006 to 2020. The young (20-24 years old) and the elderly (70-74 years old) were equally at high risk. There were differences in the age, period and cohort effects on PTB incidence among gender, urban-rural and regions. Our findings better reflected the characteristics of high-risk populations, thus contributing to the development of timely and effective intervention strategies, and providing clues for etiological research.

Developing a Subjective Evaluation Scale for Assessing the Built Environments of China's Hygienic City Initiative.

OBJECTIVE: To develop a preliminary subjective evaluation scale for assessing the built environments of China's Hygienic City Initiative and to evaluate its reliability and validity. METHODS: The initial items of the scale were determined based on a review of policy documents and consultations with experts. The final items of the scale were confirmed through individual interviews with residents combined with the discretetrend method, critical ratio method, correlation coefficient method, and factor analysis method. Then, the dimensions of the scale were determined using exploratory factor analysis (EFA). The Cronbach's α coefficient, split-half reliability coefficient, and confirmatory factor analysis (CFA) were used to assess the reliability and validity of the scale. RESULTS: A scale containing five dimensions with 22 items was established, including urban lifestyle, governance, basic functions, environmental sanitation, and amenities. The Cronbach's α coefficient of the scale was 0.876, and the split-half reliability coefficient was 0.796. The CFA results indicate that each inspection level was within the standard limit. CONCLUSION: The preliminarily subjective evaluation scale for assessing the built environments of China's Hygienic City Initiative demonstrates a high level of reliability and validity. Additional empirical studies should be carried out to further verify the value of the scale in terms of practical application.

Physical Activity and Sedentary Behaviors among Chinese Children: Recent Trends and Correlates.

OBJECTIVE: This study was aimed at examining the trends and correlates of physical activity (PA) and sedentary behaviors among Chinese children. METHODS: A total of 4,341 subjects (6,936 observations) aged 6-17 years who participated in the China Health and Nutrition Survey (2004-2015) were included. Of the subjects, 41% participated in the survey twice or more. Random-effects ordinal regression models and repeated-measures mixed-effects models were used to examine the PA trends. Quantile regression models were applied to examine the factors influencing PA and sedentary behaviors. RESULTS: From 2004 to 2015, the prevalence of physical inactivity among Chinese children aged 6-17 years increased by 5.5% [odds ratio ( OR), 1.51; 95% confidence interval ( CI), 1.19-1.90; P < 0.001]. The PA volume declined by 5.8 metabolic equivalent of task-hr/week ( P < 0.001), and the time spent in sedentary behaviors increased by 1.8 hr/week ( P < 0.001). Age, ethnicity, and region showed significant effects on the PA volume across the quartiles ( P < 0.001). Across the quartiles, sedentary time was significantly higher in the children residing in urban areas ( P < 0.001) or areas with high urbanization levels ( P ≤ 0.005) than in their counterparts. CONCLUSIONS: A declining PA trend among Chinese children aged 6-17 years was observed from 2004 to 2015, and certain subgroups and geographical areas are at higher risk of physical inactivity.

Infection control and the burden of tuberculosis infection and disease in health care workers in china: a cross-sectional study.

BACKGROUND: Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China. METHODS: A cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model. RESULTS: The assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff. CONCLUSION: TB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative measures, renovation of buildings, and use of respirators and masks. Regular screening of HCW for TB disease and LTBI needs to be considered, offering preventive therapy to those with TST conversions.

Epidemiological Characteristics of Notifiable Infectious Diseases among Foreign Cases in China, 2004-2017.

OBJECTIVE: We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases. METHODS: We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System (NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed. RESULTS: A total of 67,939 cases of 33 different infectious diseases were reported among foreigners. These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus (HIV) of 18,713 cases, hepatitis B (6,461 cases), hand, foot, and mouth disease (6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces. CONCLUSIONS: This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.

Association between Selenium in Soil and Diabetes in Chinese Residents Aged 35-74 Years: Results from the 2010 National Survey of Chronic Diseases and Behavioral Risk Factors Surveillance.

OBJECTIVE: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. METHODS: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. RESULTS: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( IQR: 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( ORs) (95% CI) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The P values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted OR (95% CI) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the P values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. CONCLUSION: Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.

High-pressure balloon dilation for male anterior urethral stricture: single-center experience.

OBJECTIVES: We retrospectively reviewed the urethral stricture cases treated in our tertiary center, and assessed the safety and feasibility of the high-pressure balloon dilation (HPBD) technique for anterior urethral stricture. METHODS: From January 2009 to December 2012, a total of 31 patients with anterior urethral strictures underwent HPBD at our center, while another 25 cases were treated by direct vision internal urethrotomy (DVIU). Patient demographics, stricture characteristics, surgical techniques, and operative outcomes were assessed and compared between the two groups. The Kaplan-Meier survival analysis was applied to evaluate the stricture-free rate for the two surgical techniques. RESULTS: The operation time was much shorter for the HPBD procedure than for the DVIU ((13.19±2.68) min vs. (18.44±3.29) min, P<0.01). For the HPBD group, the major postoperative complications as urethral bleeding and urinary tract infection (UTI) were less frequently encountered than those in DVIU (urethral bleeding: 2/31 vs. 8/25, P=0.017; UTI: 1/31 vs. 6/25 P=0.037). The Kaplan-Meier survival analysis showed that there was no significant difference in stricture-free rate at 36 months between the two groups (P=0.21, hazard ratio (HR)=0.65, 95% confidence interval (CI): 0.34 to 1.26). However, there was a significantly higher stricture-free survival in the HPBD group at 12 months (P=0.02, HR=0.35, 95% CI: 0.14 to 0.87), which indicated that the stricture recurrence could be delayed by using the HPBD technique. CONCLUSIONS: HPBD was effective and safe and it could be considered as an alternative treatment modality for anterior urethral stricture disease.

Laparoscopic colonic anastomosis using a degradable stent in a porcine model.

AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model.

Association of Chemotactic Chemokine Ligand 5 Polymorphisms with the Risk of Developing Severe Enterovirus 71 Infection.

Respiratory damage is a main manifestation of severe Enterovirus 71 (EV71) infection. Polymorphisms of -403G/A (rs2107538), -28C/G (rs2280788), and In1.1T/C (rs2280789) in chemotactic chemokine ligand 5 (CCL5) have linked with many respiratory diseases. In this study, we explored the possible correlation of CCL5 polymorphisms with severe EV71 infection. Blood samples were obtained from 87 children hospitalized for EV71 infection. Fifty-seven healthy children were enrolled as asymptomatic controls. Genotype and allele frequencies were analyzed by logistic regression analysis. There were statistically significant differences in polymorphisms of CCL5 -403G/A and In1.1T/C for dominant model (P = 0.016; P = 0.027) and additive model (P = 0.010; P = 0.019) between patients with severe EV71 infection and asymptomatic controls. With ordinal logistic regression model analysis, statistically significant differences were found between polymorphisms of CCL5 (-403G/A) (P = 0.034) with the severity of EV71 infection after adjusting for age. The frequency of A-C-C haplotype was significantly higher in EV71 infection patients than controls (P = 0.032). These results suggest that CCL5 -403G/A and In1.1T/C polymorphisms may contribute to severe EV71 infection and individuals with haplotype of A-C-C may exhibit higher risk of developing severe EV71 infection. These findings may provide insights into pathogenic and protective mechanisms of severe EV71 infection.

Recent advances in the study of testicular nuclear receptor 4.

Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4's physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4(-/-)) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4(-/-) phenotype. With the establishment of a tissue-specific TR4(-/-) mouse model, research on TR4 will be more convenient in the future.