Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis. Despite recent advances in prostate cancer treatment, some patients still experience recurrence or even progression after undergoing radical treatment. Accurate initial staging and monitoring for recurrence determine patient management, which in turn affect patient prognosis and survival. Classical imaging has limitations in the diagnosis and treatment of prostate cancer, but the use of novel molecular probes has improved the detection rate, specificity, and accuracy of prostate cancer detection. Molecular probe-based imaging modalities allow the visualization and quantitative measurement of biological processes at the molecular and cellular levels in living systems. An increased understanding of tumor biology of prostate cancer and the discovery of new tumor biomarkers have allowed the exploration of additional molecular probe targets. The development of novel ligands and advances in nano-based delivery technologies have accelerated the research and development of molecular probes. Here, we summarize the use of molecular probes in positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound imaging, and provide a brief overview of important target molecules in prostate cancer.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Molecular Probes ; Molecular Imaging/methods* ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Ultrasonography ; Optical Imaging ; Biomarkers, Tumor ; Precision Medicine/methods*

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Currently, treatment strategies for upper tract urothelial carcinoma (UTUC) are changing rapidly. However, there are many limitations in the implementation of new surgical methods and systemic treatment options, which cannot reverse the current status quo of UTUC treatment. In recent years, antibody-drug conjugates have shown great potential in the field of cancer treatment, which can activate the immune system and enhance the effect of immunotherapy while accurately killing targeted tumor cells. The results of multiple clinical trials, including the EV-302 study, have confirmed that combination therapy can improve the survival rate of patients with advanced urothelial cancer, and may replace chemotherapy as the first-line treatment for advanced urothelial cancer. However, there are still a series of challenges in the application of combination therapy in UTUC, such as low level of evidence, adverse reactions, and drug resistance. In the future, it is necessary to focus on clinical trials of UTUC combination therapy, further optimize antibody drug conjugates and immunotherapy drugs to adapt to the disease characteristics of UTUC, and further study the molecular biology characteristics of UTUC to meet this series of challenges.

Currently, treatment strategies for upper tract urothelial carcinoma (UTUC) are changing rapidly. However, there are many limitations in the implementation of new surgical methods and systemic treatment options, which cannot reverse the current status quo of UTUC treatment. In recent years, antibody-drug conjugates have shown great potential in the field of cancer treatment, which can activate the immune system and enhance the effect of immunotherapy while accurately killing targeted tumor cells. The results of multiple clinical trials, including the EV-302 study, have confirmed that combination therapy can improve the survival rate of patients with advanced urothelial cancer, and may replace chemotherapy as the first-line treatment for advanced urothelial cancer. However, there are still a series of challenges in the application of combination therapy in UTUC, such as low level of evidence, adverse reactions, and drug resistance. In the future, it is necessary to focus on clinical trials of UTUC combination therapy, further optimize antibody drug conjugates and immunotherapy drugs to adapt to the disease characteristics of UTUC, and further study the molecular biology characteristics of UTUC to meet this series of challenges.

ObjectiveBy starting with the combination of Os Draconis， Bupleuri Radix， and Ostreae Concha， the role of mineral medicine Os Draconis in the combination of the Bupleuri Radix-containing tri-herbal medicines was preliminarily explored from the perspective of supramolecular system formation. Method① The appearance and Tyndall phenomenon of single decoction of Os Draconis， Bupleuri Radix， and Ostreae Concha， as well as co-decoction of Bupleuri Radix-Os Draconis， Bupleuri Radix-Os Draconis-Ostreae Concha， and Bupleuri Radix-Ostreae Concha were observed， and the average particle size， dispersion coefficient， and Zeta potential of suspension particles in each decoction were determined. The micromorphology of supramolecular structures was observed by scanning electron microscope （SEM）. ② The pH of different compatibility systems， liquid viscosity coefficient， liquid surface tension， freeze-dried powder yield rate， and other physical properties were determined， and the interaction of different compatibility systems was detected by infrared absorption spectroscopy （FTIR） and UV-visible spectrophotometry （UV-Vis）. ③ The composition and content difference of different compatible systems were determined by high-performance liquid chromatography （HPLC） and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the single decoction， the co-decoction had more obvious turbidity and Tyndall phenomenon. The particles in the co-decoction suspension were smaller and more evenly distributed， and the Zeta potential was reduced， indicating a more stable system. Under SEM， Bupleuri Radix was irregularly lamellar， and Bupleuri Radix-Os Draconis and Bupleuri Radix-Os Draconis-Ostreae Concha were mainly spherical nanoparticles. Bupleuri Radix-Ostreae Concha was irregularly lamellar， with a small number of spherical nanoparticles. The pH of the single decoction of Bupleuri Radix and co-decoction increased， and the viscosity coefficient increased. The liquid surface tension decreased. The freeze-dried powder yield rate of the Bupleuri Radix-Os Draconis co-decoction was the highest， followed by Bupleuri Radix-Ostreae Concha decoction and Bupleuri Radix-Os Draconis-Ostreae Concha decoction， and the yield rate of Bupleuri Radix single decoction was the lowest. The main change of FTIR was the stretching vibration of -OH， and the co-decoction moved to the low-frequency direction obviously. UV-Vis showed that the maximum absorption occurred at 295.8 nm for all groups， and the absorption intensity was different （Bupleuri Radix-Os Draconis>Bupleuri Radix-Os Draconis-Ostreae Concha>Bupleuri Radix-Ostreae Concha>Bupleuri Radix）. The components of Bupleuri Radix were used as the indexes， and the content of methanol extract determined by HPLC was higher than that of water extract， and the components of Bupleuri Radix single decoction were mainly saikosaponin a （SSa） and saikosaponin c （SSc）， which were slightly higher after co-decoction compatibility. UPLC-Q-TOF-MS could identify 37 compounds in both single decoction and co-decoction. ConclusionThe combination of Bupleuri Radix， Os Draconis， and Ostreae Concha can form a smaller， more uniform， and stable nano-sized supramolecular system， which is conducive to the dissolution of the main components of Bupleuri Radix， and the Os Draconis contributes the most in this process.

BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

[Purpose]To analyze the incidence trend and age at diagnosis of thyroid cancer in can-cer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The continuous and com-plete cancer data from 2009 to 2019 meeting quality control requirements were collected from 16 registries in Jiangsu Province.Thyroid cancer was coded as C73 according to ICD-10.The crude incidence rate,age-standardized incidence rate by Chinese standard population(ASIRC),the mean diagnostic age and adjusted mean diagnostic age of thyroid cancer were calculated by sex,age groups and regions.The trends of above indicators were analyzed and the average annual per-centage change(AAPC)was calculated.[Results]The crude incidence rate and ASIRC of thyroid cancer for men in Jiangsu cancer registration areas in 2009 and 2019 were 1.25/105,1.00/105 and 7.32/105,6.48/105,respectively.For women those were 3.64/105,3.06/105 and 24.91/105,20.94/105,respectively.The AAPC of crude incidence rate and ASIRC of thyroid cancer from 2009 to 2019 were 22.05％(95％CI:19.70％～24.45％)and 22.55％(95％CI:20.06％～25.08％),respectively.The adjusted mean diagnostic age of thyroid cancer declined from 46.27 years old in 2009 to 43.03 years old in 2019(β=-0.243,P＜0.001).[Conclusion]The incidence rate of thyroid cancer showed an increasing trend in cancer registration areas of Jiangsu Province from 2009 to 2019,while the diagnostic age showed a downward trend during the same period.

Pharmacy services in grassroots medical institutions provide professional pharmacy services for patients. This service not only expanded the scope of primary care delivery, but also meets the residents′need for appropriate medication. At present, the majority of grassroots medical institutions in China provide outpatient pharmacy services by means of pharmacy service alliance, and foreign grassroots medical institutions mainly provide pharmaceutical outpatient services with drug treatment management as the core for patients by granting pharmacists partial prescription rights.In recent years, pharmaceutical outpatient services in grassroots medical institutions had achieved good results in improving patient clinical outcomes, enhancing medication rationality, and enhancing patient compliance. However, there were many unresolved issues, including low public awareness, shortage of pharmaceutical talents, and imperfect guarantee systems. The author suggestted that efforts should be made to increase the publicity of pharmaceutical outpatient services, improve the training mechanism for pharmacists, strengthen cooperation between pharmacists and clinical physicians, include pharmacists in the contracted service team of family doctors, and improve various guarantee systems, in order to provide reference for promoting the sustainable development of pharmaceutical outpatient services in grassroots medical institutions in China.