BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.

Objective:To evaluate the effect of health science popularization in child caregivers by using social media of WeChat and Weibo in China in 2020.Methods:A questionnaire was designed based on the knowledge of children health from January to March 2020, and the public were invited to participate in the survey by visiting the official accounts of WeChat and Weibo of China CDC to analyze the awareness of health related knowledge and the change of daily behaviors in the child caregivers.Results:In the 1 325 child caregivers included in this survey, the awareness rate of chronic disease reexamine was lowest (74.94%), and the awareness rate of quality-oriented education was highest (99.55%). In the 7 questions in the questionnaire, the correct answer rate of the question about the reexamine of chronic disease was <75.00% (below the standard), the correct answer rate to other six questions were all ≥75.00% (above the standard). Logistic regression analysis showed that the education levels of senior high school or technical secondary school, junior college, bachelor's degree, master's degree or above, being worker, business/service personnel, teacher and company employee were the influencing factors for the awareness of the chronic disease related knowledge in child caregivers (all P<0.05). The daily behaviors of child caregivers after acquiring health knowledge were significantly improved (all P<0.001). Conclusions:In the season with high incidence of respiratory diseases, the use of new media platforms, such as WeChat and Weibo, to conduct health education had a good performance, resulting in higher rate of knowledge about healthy parenting and a significant improvement in daily behaviors in child caregivers. The results showed that the health education about the reexamine of chronic diseases in children should be focused on child caregivers with low education level, especially workers, business/service personnel.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Objective:To investigate the application value of contrast-enhanced ultra-sound, enhanced computed tomography (CT) and enhanced magnetic resonance imaging (MRI) in the diagnosis of small hepatocellular carcinoma.Methods:The clinical diagnositic trial was con-ducted. The clinicopathological data of 145 patients with small hepatocellular carcinoma who were admitted to the First Affiliated Hospital of Amy Medical University from January 2019 to June 2021 were collected. There were 121 males and 24 females, aged from 26 to 78 years, with a median age of 54 years. All patients were examined with contrast-enhanced ultrasound, enhanced CT and enhanced MRI, and underwent surgical resection of liver lesions within one month. Observation indicators: (1) postoperative histopathological examinations of patients with small hepatocellular carcinoma; (2) examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (3) imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (4) enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (5) the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the Cochran′s Q test or the chi-square test. The sensitivity, specificity and accuracy were used to analyze the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Results:(1) Postoperative histopathological examinations of patients with small hepatocellular carcinoma. There were 154 lesions detected in the postoperative histopathological examinations for the 145 small hepatocellular carcinoma patients, with the tumor diameter as (2.2±0.6)cm. (2) Examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI. There were 153, 154 and 154 lesions detected in contrast-enhanced ultrasound, enhanced CT and enhanced MRI for the 145 patients with small hepatocellular carcinoma, respectively, with the detection rate as 99.35%(153/154), 100.00%(154/154) and 100.00%(154/154), showing no significant difference among the 3 imaging examination methods ( Q=2.00, P>0.05). (3) Imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, 140 lesions showed "fast-in and fast-out" enhancement, 12 lesions showed "fast-in and slow-out" enhancement and 1 lesion showed isoenhancement in arterial phases and hypoenhancement in portal and delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, 112 lesions showed "fast-in and fast-out" enhancement, 13 lesions showed "fast-in and slow-out" enhancement, 14 lesions showed isoenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed hypoenhancement in the three phases, 3 lesions showed hyperenhancement in the three phases, 1 lesion showed isoenhancement in the three phases and 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, 134 lesions showed "fast-in and fast-out" enhancement, 1 lesion showed "fast-in and slow-out" enhancement, 8 lesions showed isoenhancement in arterial phase and hypoenhance-ment in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delay phases, 2 lesions showed rim-like hyperenhancement in the three phases, 1 lesion showed hyperenhancement in the three phases, 1 lesion showed hypoenhancement in the three phases, 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed late phase, 1 lesion showed edge delay enhancement in the three phases. (4) Enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 152 lesions with hyperenhancement and 1 lesion with iso or hypoenhance-ment in the arterial phase, there were 55 lesions with hyper or isoenhancement and 98 lesions with hypoenhancement in the portal venous phase, there were 12 lesions with hyper or isoenhancement and 141 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, there were 133 lesions with hyperen-hancement signal and 21 lesions with iso or hypoenhancement in the arterial phase, there were 53 lesions with hyper or isoenhancement and 101 lesions with hypoenhancement in the portal phase, there were 17 lesions with hyper or isoenhancement and 137 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, there were 143 lesions with hyperenhancement and 11 lesions with iso or hypoenhance-ment in the arterial phase, there were 29 lesions with hyper or isoenhancement and 125 lesions with hypoenhancement in the portal phase, there were 5 lesions with hyper or isoenhancement and 149 lesions with hypoenhancement in the delayed phase. There were significant differences in the enhancement mode distribution of lesions in the arterial, portal and delayed phases among contrast-enhanced ultrasound, enhanced CT and enhanced MRI ( χ2=19.47, 13.21, 6.92, P<0.05). (5) The efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 3 lesions misdiagnosed according to the postoperative histopathological examinations. Of the 154 lesions reported in enhanced CT and enhanced MRI for patients with small hepatocellular carcinoma, there were 7 lesions and 2 lesions misdiagnosed according to the postoperative histopathological examinations, respectively. Lesions misdiagnosed in one imaging examination method were correctly diagnosed in the other two imaging examination methods. The sensitivity, specificity, accuracy were 97.4%, 63.0%, 92.3% for contrast-enhanced ultrasound in the diagnosis of small hepatocellular carcinoma. The above indica-tors were 95.5%, 63.0%, 90.6% for enhanced CT and 98.7%, 63.0%, 93.4% for enhanced MRI in the diagnosis of small hepatocellular carcinoma. There was no significant difference in the sensitivity and accuracy among the 3 imaging examination methods ( Q=2.92, 0.00, 1.81, P>0.05). Conclusion:Contrast-enhanced ultrasound, enhanced CT and enhanced MRI all have good diagnostic value in diagnosis of small hepatocellular carcinoma, and they complement each other.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.