Prostate cancer is one of the most common malignant tumor of male population in the West.Via binding to androgen response element in the genome and interacting with co-regulators,androgen receptor can participate in the development of prostate cancer and the convertion from androgen dependent prostate cancer to androgen independent prostate cancer.Chromatin immunoprecipitation ,coupled with PCR , chip,and high-throughput sequencing ,makes a huge progress in the study on the downstream target genes of androgen receptor and provide a new way to understand the molecular mechanisms of castration -resistant prostate cancer.

Objective To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid ( 8-OHdG) in the diagnosis of nonalcoholic steatohepatitis ( NASH).Methods Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People ′s Hospital of Tianjin from May 2013 to December 2015.A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study , including 20 nonalcoholic simple fatty liver ( NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy.The other 32 healthy subjects were studied as controls.Serum 8-OHdG, ALT, AST and GGT were tested.Nonalcoholic fatty liver disease activity score ( NAS ) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients.The correlations between serum 8-OHdG and serum ALT , AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated.In addition , the receiver operating characteristic ( ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients , and the cut-off value was determined.Results Serum 8-OHdG values in healthy controls , NAFL and NASH patients were (0.19 ±0.16) μg/L, (0.22 ±0.16) μg/L, (0.42 ±0.21) μg/L respectively.The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6.AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L.Its sensitivity was 88.3%and specificity was 81.5%, which were higher than those of ALT.Conclusion The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.

Objective:To analyze the current level and dynamic change of the salary and income satisfaction rate of doctors in Chinese tertiary public hospitals in recent years.Methods:In January 2018, March 2019 and March 2021, the project team of " the third party evaluation of the China Healthcare Improvement Initiative" conducted a questionnaire survey among doctors of 136 tertiary public hospitals in 31 provinces. The first-line clinicians were investigated by stratified sampling method. The salary level and satisfaction of doctors were investigated by questionnaire. Chi square test was used for comparison between groups.Results:The sample size of the three surveys was 20 786, 23 289 and 22 836 respectively. The median value of doctors′ actual income after tax in 2017, 2018 and 2020 was 100 800 yuan, 120 000 yuan, 150 000 yuan respectively, and the median expected annual income after tax was 196 000 yuan, 250 000 yuan and 250 000 yuan. The proportion of doctors satisfied with the current income was 16.5%, 17.8% and 26.9% respectively. The salary and satisfaction rate of doctors had an upward trend, but the overall level was still low.Conclusions:In recent years, the salary of doctors in tertiary public hospitals in China has been improved to a certain extent, but on the whole, it is at a low level, and there is still much room for improvement. In the future, the government needs to improve the hospital salary system and increase the salary of doctors continuously, especially needs to pay attention to the doctors with high education level and intermediate titles.

Objective:To investigate the value of surgical classification and pelvic floor reconstruction in pelvic exenteration for locally recurrent or locally advanced rectal cancer. Methods:A retrospective descriptive study method was used.Perioperative data were collected from 67 consecutive patients with locally advanced or locally recurrent rectal cancer who underwent pelvic exenteration at the Department of Anorectal Surgery,the Second Affiliated Hospital of Navy Military Medical University between November 2021 and November 2022 through the Chinese Combined Pelvic Exenteration Case Database for rectal cancer.The surgical range was divided into two categories:mainly localized in the pelvic cavity(48 cases)and combined with resection of the main tissue of the pelvic wall(1 9 cases).Outcome indexes included:(1)preoperative general data of patients;(2)intraoperative conditions;(3)postoperative recovery and complications(postoperative complications were evaluated by international Clavien-Dindo classification);(4)follow-up(outpatient and telephone follow-up were used to understand the postoperative survival,tumor recurrence and metastasis of patients,and the follow-up time was up to February 28,2023 or the case died).Measurement data are expressed by median(range),and enumeration data are expressed by example(％). Results:In the pelvic resection group,the median age of 48 patients was 57.5 years(range:31-82 years);29 were males and 19 were females;26 of them had locally advanced rectal cancer and 22 had locally recurrent rectal cancer;39 had a history of chemotherapy,immunotherapy or targeted therapy,and 26 had a history of radiotherapy;the median operation time was 425 min(range:240-1 020 min);the median intraoperative blood loss was 500 mL(range:200-4 000 mL);the median time to recovery of intestinal function was 3 d(range:1-9 d);the median recovery time of empty pelvis syndrome was 25.3 d(range:5-105 d);43 patients had postoperative complications＜grade Ⅲ,and of the 5 patients with ≥ grade Ⅲcomplications,2 died of multiple organ failure 7 d after operation,2 patients had surgical hemostasis for massive hemorrhage of pelvic floor wounds after operation,and 1 patient recovered from postoperative respiratory failure after rescue.In the combined pelvic wall resection group,the median age of 1 9 patients was 54.5 years(range:43-76 years);9 were males and 10 were females;4 patients had locally advanced rectal cancer and 15 patients had locally recurrent rectal cancer,all of whom had a history of chemotherapy,immunotherapy or targeted therapy,and 1 5 patients had a history of radiotherapy;the median operation time was 580 min(range:360-960 min);the median intraoperative blood loss was 1 600 mL(range:400-4 000 mL);the median intestinal function recovery time was 3 d(range:2-7 d);the median empty pelvis syndrome recovery time was 62.3 d(range:7-120 d);15 patients had postoperative complications＜grade Ⅲ,and of the 4 patients with grade ≥ Ⅲ,3 patients had surgical hemostatis for postoperative pelvic floor wound bleeding and 1 patient recovered after the second operation for intestinal obstruction.As of February 28,2023 or death,67 patients were followed up for a median of 7.5 months(range:3-1 5 months),and 3 patients died 3-8 months after operation due to rapid tumor progression,severe urinary tract infection,and sudden heart disease during the follow-up period.The remaining 62 cases survived. Conclusion:The surgical classification has guiding significance for preoperative surgical planning in patients with locally advanced or locally recurrent rectal cancer who undergo combined pelvic exenteration,and the method of pelvic floor reconstruction based on biological mesh is safe and feasible in combined pelvic exenteration for locally advanced or locally recurrent rectal cancer.

Objective To investigate the acute toxicology and intervention effect of Panacis Majoris Rhizoma on rats with chronic pharyngitis.Methods A single,maximum dose of Panacis Majoris Rhizoma(74.4 g·kg-1)was administered to Kunming mice to evaluate its toxicity,involving the assessment of the survival status of the mice,organ indices,morphological changes in major organs,blood routine,and biochemical indicators.SD rats were randomly divided into the control group,model group,prednisone group(6.25 mg·kg-1),and low-,medium-,and high-dose Panacis Majoris Rhizoma groups(0.58,1.16,and 2.32 g·kg-1).All rats received the corresponding drugs(or normal saline)via intragastric administration once daily for a duration of 30 days.Except the control group,chronic pharyngitis was induced in rats of the other groups by using β-hemolytic streptococcus.Following euthanasia,serum inflammatory levels of interleukin-6(IL-6),cyclooxygenase-2(COX-2),interleukin-1β(IL-1β),intercellular adhesion molecule-1(ICAM-1),C-reactive protein(CRP),tumor necrosis factor(TNF-α),monocyte chemoattractant protein-1(MCP-1),and prostaglandin E2(PGE2)were measured.Additionally,pharyngeal tissues were stained with HE and pathological characteristics were observed.Results Toxicological studies have demonstrated that the administration of Panacis Majoris Rhizoma resulted in significant increase in plasma alanine transaminase levels and spleen index of mice,along with corresponding tissue pathological alterations.Nevertheless,no noteworthy pathological changes were observed in other organs,and there were no notable changes in blood routine and plasma biochemical indicators.Pharmacodynamic investigations have revealed that Panacis Maioris Rhizoma effectively reduces the serum levels of inflammatory factors and improves pathological changes in pharyngeal tissues.Conclusion Panacis Maioris Rhizoma alleviated β-hemolytic streptococcus-induced CP by inhibiting inflammatory responses,and may show potential toxicity to the spleen.

Objective:To investigate the radiosensitizing effect of silencing breast cancer susceptibility gene 1 (shBRCA1) expression on MDA-MB-231 breast cancer bearing nude mice by 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT) microPET/CT imaging. Methods:Twenty-four BALB/c nude mice were divided into 4 groups ( n=6 in each group) according to the random number table method, namely negative control (NC) group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group. 18F-FLT microPET/CT imaging was performed before and 24 h after radiotherapy. The changes of SUV max before and after radiotherapy were compared among 4 groups, and the total proliferative volume (TPV) of tumors in each group after treatment was also analyzed. The expression of Ki-67 in tumor tissues was analyzed by immunohistochemistry. Data were analyzed by paired t test, one-way analysis of variance, least significant difference t test and Pearson correlation analysis. Results:Breast cancer cells targeting the BRCA1 were constructed. Before radiotherapy, the differences of SUV max among the NC group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group were not statistically significant (1.034±0.137, 1.031±0.152, 1.028±0.169 and 1.026±0.156; F=0.00, P=0.999). Twenty-four hours after the end of the four times of radiotherapy, the differences of SUV max among the 4 groups were statistically significant (1.367±0.100, 0.781±0.079, 1.306±0.213 and 0.597±0.129; F=44.77, P<0.001), with lower SUV max in the shBRCA1+ radiotherapy group compared with the NC+ radiotherapy group ( t=2.98, P=0.014). The SUV max of the NC+ radiotherapy group and shBRCA1+ radiotherapy group were reduced compared with those before radiotherapy ( t values: 5.82, 5.44, P values: 0.002, 0.003), while SUV max of the NC group and shBRCA1 group increased compared with those before radiotherapy ( t values: -4.47, -3.98, P values: 0.007, 0.011). TPV was smaller in the shBRCA1+ radiotherapy group compared with that in the NC+ radiotherapy group (0.48±0.03 vs 0.61±0.07; F=25.36, t=3.82, P=0.003). Immunohistochemical assays showed that Ki-67 was less expressed in the shBRCA1+ radiotherapy group than that in the NC+ radiotherapy group (0.286±0.072 vs 0.476±0.093; F=15.73, t=3.61, P=0.007). Correlation analysis showed a positive correlation between Ki-67 expression and SUV max ( r=0.83, P<0.001). Conclusion:18F-FLT microPET/CT imaging can evaluate the radiosensitizing effect of shBRCA1 expression on MDA-MB-231 breast cancer bearing nude mice.

To provide a theoretical basis for controlling the spread of rust disease, cultivating disease-resistant varieties and reducing yield losses, we investigated the transcriptome differences between Gymnosporangium yamadae and Gymnosporangium asiaticum at the haustorial stage and revealed a specialized selection mechanism for Gymnosporangium species to infect host plants. We sequenced the transcriptomes of the haustoria in rust-infected leaves when basidiospores of G. yamadae and G. asiaticum infected their hosts, and obtained 21 213 and 13 015 unigenes, respectively. Real-time fluorescence quantitative PCR validation of five genes selected from G. yamadae and G. asiaticum, respectively, showed that their expression profiles were generally consistent with the results of transcriptome analysis, demonstrating the reliability of the transcriptome data. We used seven databases such as Nr, GO, KEGG, and KOG to perform gene function annotation and enrichment analysis, and found that the genes from both rusts were mainly enriched in cellular processes, translation, and metabolism-related pathways. Moreover, we used SignalP, TMHMM online website and other software such as dbCAN, BLSAT, HMMER to show that there were 343 (2.51%) and 175 (2.79%) candidate effector proteins containing 14 and 5 proteases and 10 and 3 lipases in the haustoria of G. yamadae and G. asiaticum, respectively. Furthermore, we used OrthoFinder, BLAST and KaKs Calculator software to analyze the evolutionary relationship of the two fungi. Among one-to-one homologous genes, gene pairs with > 82% alignment were considered to be under conservative selection, and 12.37% under positive selection. Five effectors of G. asiaticum were under positive selection, and one of which was a lipase. No significant differences were found in the enrichment of expressed genes between G. yamadae and G. asiaticum, indicating the biological processes involved in haustoria were relatively conserved, despite the typical host selectivity between species. The low protein similarity between the two species suggested that they were under greater host selective pressure and there was significant evolutionary divergence, which might be related to the host-specific selection mechanism. In the haustorial, the main purpose of the effectors might be to regulate physiological processes in the plants rather than attacking the host directly, and G. yamadae and G. asiaticum might use plant lipids as energy sources.
Transcriptome ; Reproducibility of Results ; Plant Diseases/microbiology* ; Gene Expression Profiling/methods*

Objective:To review the scope of related factors that affect the elderly′s participation in digital health intervention, and to provide a certain reference for the application and development of smart elderly technology.Methods:Based on the scope review guidelines issued by the Joanna Briggs Institute in Australia in 2019, the inclusion and exclusion criteria were determined according to the PCCS principles. Chinese and English literatures were searched in PubMed, Cochrane Library, JBI, CINAHL, Web of Science, Scopus, CNKI, Wanfang database and Chinese biomedical literature database. The search time limit was from the establishment of the database to November 30, 2021. Two researchers independently read, and used EndNoteX9 and Excel tables to extract relevant data from the literature for summary and analysis.Results:Totally 20 articles were selected, including 2 mixed studies, 10 cross-sectional studies, 6 qualitative studies, and 2 quasi-experimental studies. Relevant factors affecting the participation of the elderly in digital health interventions involved the developers, users and the user himself of digital health intervention systems, including the degree of system integration of system development, the degree of autonomy of the elderly, the credibility and accessibility of system equipment and ease of use; the degree of compatibility of equipment in the process of use, the degree of digital infrastructure configuration, the degree of Internet penetration, the availability and reliability of health information resources, the degree of training and education, the degree of communication with the elderly in the process of participation, financial payment, etc.; the four inherent factors of the elderly included the cost of technology use, technical anxiety, privacy and safety, and health needs.Conclusions:The elderly, medical staff, developers and other stakeholders should jointly participate in decision-making on the development and management of the digital health intervention system for the elderly, especially by inviting and empowering the elderly , and improve the training and feedback of the system application and use process, accelerate the popularization and promotion of technical resources, and increase social capital and financial payment incentives to reduce the burden on the elderly and the medical system.

Objective: To investigate the effect of 18 F-deoxythymidine nucleoside ( 18 F-FLT) positron emission computed tomography (PET / CT) imaging to evaluate the radiosensitization effect of Olaparib on breast cancer model in nude mice． Methods : According to the random number table method，twenty-four BALB / C nude mice MCF- 7 breast cancer models were established and divided into four groups with 6 mice in each group，namely the control group，radiotherapy group，Olaparib group and Olaparib + radiotherapy group． 18 F-FLT micro PET / CT imaging was performed on nude mice before and 48 h after treatment，respectively．The changes of maximum standardized uptake value ( SUVmax ) ，total proliferation volume (TPV) and tumor volume before and after tumor treatment in four groups were compared．The tumors were extracted and weighed to observe the changes of tumor weight，and the expression of Ki-67 and PCNA was analyzed by immunohistochemistry staining．The correlation of tumor SUVmax with Ki-67 and PCNA was analyzed. Results : Before treatment，there were no significant differences in SUVmax ， TPV and tumor volume among the 4 groups (F = 0. 041，0. 061，0. 045，P＞0. 05) ．48 h after treatment，SUVmax in the control and Olaparib groups increased significantly ( t = －12. 111，P ＜0. 001 ; t = －3. 001，P = 0. 03 ) ， SUVmax was reduced in the radiotherapy and Olaparib + radiotherapy groups (t = 5. 829，P＜0. 01 ; t = 4. 448，P < 0. 01) ，while SUVmax ，TPV and tumor volume of tumors in the Olaparib + radiotherapy group were lower than those in the radiotherapy group (t = 3. 388，5. 884，5. 990，P＜0. 01) ．Tumor weight was significantly lower in the Olaparib + radiotherapy group than in the other three groups ( F = 44. 405，P ＜0. 001 ) ． Immunohistochemical staining showed that Ki-67 and PCNA were the least expressed in the Olaparib + radiotherapy group than in the other three groups (F = 16. 289，39. 645，P＜0. 001) ．SUVmax was positively correlated with Ki-67 and PCNA expression (r = 0. 920，0. 918，P＜0. 01) ． Conclusion 18 F-FLT Micro PET / CT imaging can evaluate the radiosensitizing effect of Olaparib on nude mouse breast cancer model.

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.