Incidence, temporal trends and risk factors of puerperal infection in Mainland China: a meta-analysis of epidemiological studies from recent decade (2010-2020).

BACKGROUND: Puerperal infection (PI) is a severe threat to maternal health. The incidence and risk of PI should be accurately quantified and conveyed for prior decision-making. This study aims to assess the quality of the published literature on the epidemiology of PI, and synthesize them to identify the temporal trends and risk factors of PI occurring in Mainland China. METHODS: This review was registered in PROSPERO (CRD42021267399). Putting a time frame on 2010 to March 2022, we searched Cochrane library, Embase, Google Scholar, MEDLINE, Web of Science, China biology medicine, China national knowledge infrastructure and Chinese medical current contents, and performed a meta-analysis and meta-regression to pool the incidence of PI and the effects of risk factors on PI. RESULTS: A total of 49 eligible studies with 133,938 participants from 17 provinces were included. The pooled incidence of PI was 4.95% (95%CIs, 4.46-5.43), and there was a statistical association between the incidence of PI following caesarean section and the median year of data collection. Gestational hypertension (OR = 2.14), Gestational diabetes mellitus (OR = 1.82), primipara (OR = 0.81), genital tract inflammation (OR = 2.51), anemia during pregnancy (OR = 2.28), caesarean section (OR = 2.03), episiotomy (OR = 2.64), premature rupture of membrane (OR = 2.54), prolonged labor (OR = 1.32), placenta remnant (OR = 2.59) and postpartum hemorrhage (OR = 2.43) have significant association with PI. CONCLUSIONS: Maternal infection remains a crucial complication during puerperium in Mainland China, which showed a nationwide temporal rising following caesarean section in the past decade. The opportunity to prevent unnecessary PI exists in several simple but necessary measures and it's urgent for clinicians and policymakers to focus joint efforts on promoting the bundle of evidence-based practices.

Vacuolar Sugar Transporter TMT2 Plays Crucial Roles in Germination and Seedling Development in Arabidopsis.

Vacuolar sugar transporters transport sugar across the tonoplast, are major players in maintaining sugar homeostasis, and therefore play vital roles in plant growth, development, and biomass yield. In this study, we analyzed the physiological roles of the tonoplast monosaccharide transporter 2 (TMT2) in Arabidopsis. In contrast to the wild type (WT) that produced uniform seedlings, the tmt2 mutant produced three types of offspring: un-germinated seeds (UnG), seedlings that cannot form true leaves (tmt2-S), and seedlings that develop normally (tmt2-L). Sucrose, glucose, and fructose can substantially, but not completely, rescue the abnormal phenotypes of the tmt2 mutant. Abnormal cotyledon development, arrested true leaf development, and abnormal development of shoot apical meristem (SAM) were observed in tmt2-S seedlings. Cotyledons from the WT and tmt2-L seedlings restored the growth of tmt2-S seedlings through micrografting. Moreover, exogenous sugar sustained normal growth of tmt2-S seedlings with cotyledon removed. Finally, we found that the TMT2 deficiency resulted in growth defects, most likely via changing auxin signaling, target of rapamycin (TOR) pathways, and cellular nutrients. This study unveiled the essential functions of TMT2 for seed germination and initial seedling development, ensuring cotyledon function and mobilizing sugars from cotyledons to seedlings. It also expanded the current knowledge on sugar metabolism and signaling. These findings have fundamental implications for enhancing plant biomass production or seed yield in future agriculture.

Efficient multi-LED dimming control scheme with space-time codes for VLC systems.

Visible light communication is a kind of wireless communication that combines illumination and communication, so dimming control is an essential function for visible light communication systems. Although many dimming control schemes have been proposed, few simultaneously utilize amplitude and spatial resources. The combination of these two resources can further improve the communication performance of the system. Thus, we propose a dimming control scheme that takes advantage of phase-shifted space-time codes to improve error performance and spectral efficiency. Additionally, we provide an encoding structure and a fast detection algorithm for the proposed scheme. Finally, simulation results show the performance of the proposed scheme compared with other schemes.

A Framework for an Intelligent and Personalized Fire Evacuation Management System.

Many research studies have focused on fire evacuation planning. However, because of the uncertainties in fire development, there is no perfect solution. This research proposes a fire evacuation management framework which takes advantage of an information-rich building information modeling (BIM) model and a Bluetooth low energy (BLE)-based indoor real-time location system (RTLS) to dynamically push personalized evacuation route recommendations and turn-by-turn guidance to the smartphone of a building occupant. The risk score (RS) for each possible route is evaluated as a weighted summation of risk level index values of all risk factors for all segments along the route, and the route with the lowest RS is recommended to the evacuee. The system will automatically re-evaluate all routes every 2 s based on the most updated information, and the evacuee will be notified if a new and safer route becomes available. A case study with two testing scenarios was conducted for a commercial office building in Tianjin, China, in order to verify this framework.

A Pyrolysis-Free Covalent Organic Polymer for Oxygen Reduction.

Highly efficient electrocatalysts derived from metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) for oxygen reduction reaction (ORR) have been developed. However, the subsequent pyrolysis is often needed owing to their poor intrinsic electrical conductivity, leading to undesirable structure changes and destruction of the original fine structure. Now, hybrid electrocatalysts were formed by self-assembling pristine covalent organic polymer (COP) with reduced graphene oxide (rGO). The electrical conductivity of the hybridized COP/rGO materials is increased by more than seven orders of magnitude (from 3.06×10-9 to 2.56×10-1  S m-1 ) compared with pure COPs. The ORR activities of the hybrid are enhanced significantly by the synergetic effect between highly active COP and highly conductive rGO. This COP/rGO hybrid catalyst exhibited a remarkable positive half-wave (150 mV).

[Clinicopathological features of primary seminal vesicle adenocarcinoma: A report of 4 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis, and treatment of primary seminal vesicle adenocarcinoma (SVAC). METHODS: We analyzed the clinical data and clinicopathological characteristics of 4 cases of primary SVAC treated in the Department of Urology of the Second Hospital of Tianjin Medical University and reviewed relevant literature. RESULTS: All the 4 patients were treated by open radical resection of the seminal vesicle and prostate and pathologically diagnosed with SVAC. Preoperative prostatic biopsy had shown 1 of the cases to be negative, while preoperative CT and transrectal ultrasound had revealed a huge pelvic cystic neoplasm in another patient. Immunohistochemistry manifested that the 4 cases were all negative for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and cytokeratin 20 (CK20), but positive for cancer antigen 125 (CA125) and CK7. All the patients recovered smoothly after surgery and experienced no recurrence or metastasis during 154, 41, 20, and 12 months of follow-up. CONCLUSIONS: Primary seminal vesicle carcinoma is extremely rare and presents in an advanced stage. Immunohistochemistry plays a valuable role in its differential diagnosis. Various combinations of radical surgery, radiotherapy, androgen-deprivation therapy, and chemotherapy are recommended for the treatment of the disease.

Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer.

BACKGROUND Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. MATERIAL AND METHODS We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. RESULTS We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. CONCLUSIONS Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese.

Influence of multiple spatiotemporal resolutions on the performance of urban growth simulation models.

The study developed a framework to investigate the impact of multiple spatial and temporal resolutions on urban growth simulation. The research utilized the convolutional long short-term memory (ConvLSTM) model and three regular models and data from 2009 to 2017 to simulate the urban area of Liangjiang New District in 2018 and determine the optimal spatiotemporal resolution for urban expansion models. The results indicated that the ConvLSTM model has the best simulation result and the ideal temporal resolution for Liangjiang district is to include the previous two years of data, with an optimal spatial resolution of 90 m and a spatiotemporal simulation zone within a two-year time step and 100 × 100 spatial information filter. At this combination, the kappa value of the ConvLSTM is 0.87 which is about 5% higher than others. Our findings revealed that the characteristics of input data can have a significant impact on simulation results and should be carefully considered during the simulation process.

Na-Ru bimetallic functional sites promote photo-driven CO2 directed conversion into CH4.

Recently, there has been a significant increase in interest in using photocatalysis for the energy conversion of polluting gases. In this research, sodium and ruthenium bimetallic functional sites co-modified bismuth tungstate (Ru/Na-Bi2WO6) nanoflower photocatalyst was synthesized via the hydrothermal method. The CO2 reduction products on the Bi2WO6 substrate were CO (1.66 µmol/g/h, 68 %) and CH4 (0.78 µmol/g/h, 32 %). After optimization, a significant change in the CO2 products of the Bi2WO6-based composite material was observed, with CO (0.61 µmol/g/h, 3.6 %) and CH4 (16.1 µmol/g/h, 96.4 %). Results showed that the dominance of CH4 as the main product in the Ru/Na-BWO system is attributed to the effective doping of Na, which generates impurity energy levels composed of oxygen vacancies, lowering the conduction band position of Bi2WO6, thereby suppressing CO generation, and enhancing CH4 selectivity by changing the CO2 activation pathway. The remarkable performance is ascribed to the synergized adsorption and activation of CO2 by the tandem Na+ sites and Ru0 sites. Specifically, the doped Na+ sites play a major role in promoting the adsorption CO2 molecules, while the Ru0 sites play a dominant role in facilitating the activation of the intermediates.

TNIK drives castration-resistant prostate cancer via phosphorylating EGFR.

The development of castration-resistant prostate cancer (CRPC) is driven by intricate genetic and epigenetic mechanisms. Traf2- and Nck-interacting kinase (TNIK) has been reported as a serine/threonine kinase associated with tumor cell proliferation or unfavorable cancer behavior. The microarray approach revealed a substantial upregulation of TNIK expression levels, enabling us to investigate the functional behaviors of the TNIK gene in CRPC. Specifically, we discovered that AR suppresses TNIK gene transcription in LNCaP and C4-2 cells by forming a complex with H3K27me3. Following the reduction of AR levels induced by androgen deprivation therapy (ADT), TNIK is recruited to activate EGFR signaling through phosphorylation in C4-2 cells, thereby promoting CRPC progression. Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC.

A prediction model based on random survival forest analysis of the overall survival of elderly female papillary thyroid carcinoma patients: a SEER-based study.

OBJECTIVE: Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC. METHODS: We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model. RESULTS: The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients. CONCLUSIONS: The RSF model we developed performed better than the Cox model and might be valuable for clinical practice.

Reassortant H9N2 canine influenza viruses containing the pandemic H1N1/2009 ribonucleoprotein complex circulating in pigs acquired enhanced virulence in mice.

The reassortment between avian H9N2 and Eurasian avian-like (EA) H1N1 viruses may have potentially changed from avian-to-mammals adaptation. This study generated 20 reassortant viruses with the introduction of H1N1/2009 internal genes from EA H1N1 virus into H9N2 virus. 12 of these recovered the replication capability both in the lungs and turbinate samples. 10 of 12 obtained PA gene segments from the ribonucleoprotein (RNP) complexes of the EA H1N1 virus, and 3 exhibited extreme virulence. Specially, the combination of PB2, PA and NP genes could overcome the species-specific restriction in human cells. Analysis of the polymerase activities found that introduction of the PA gene resulted in increased polymerase activity. These findings indicated that RNP complexes from EA H1N1 virus could confer an adaptation advantage and high compatibility to avian H9N2 virus. This raises new concerns for public health due to the possible coexistence of H9N2 and EA H1N1 viruses in dogs.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

Research on multi-strategy improved sparrow search optimization algorithm.

To address the issues with inadequate search space, sluggish convergence and easy fall into local optimality during iteration of the sparrow search algorithm (SSA), a multi-strategy improved sparrow search algorithm (ISSA), is developed. First, the population dynamic adjustment strategy is carried out to restrict the amount of sparrow population discoverers and joiners. Second, the update strategy in the mining phase of the honeypot optimization algorithm (HBA) is combined to change the update formula of the joiner's position to enhance the global exploration ability of the algorithm. Finally, the optimal position of population discoverers is perturbed using the perturbation operator and levy flight strategy to improve the ability of the algorithm to jump out of local optimum. The experimental simulations are put up against the basic sparrow search algorithm and the other four swarm intelligence (SI) algorithms in 13 benchmark test functions, and the Wilcoxon rank sum test is used to determine whether the algorithm is significantly different from the other algorithms. The results show that the improved sparrow search algorithm has better convergence and solution accuracy, and the global optimization ability is greatly improved. When the proposed algorithm is used in pilot optimization in channel estimation, the bit error rate is greatly improved, which shows the superiority of the proposed algorithm in engineering application.

Predictive value of serum proteomic biomarkers for noise-induced hearing loss.

Early detection of noise-induced hearing loss (NIHL) in patients with long-term noise exposure is vital for improving public health and reducing social burden. However, at present, the diagnosis of NIHL mainly depends on audiometric testing, and the primary test is pure-tone audiometry. Moreover, testing requires professional operators and complex equipment; thus, NIHL is often diagnosed at a later disease stage. Using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic approach, we identified 9 differentially expressed proteins (DEPs), namely, 6 upregulated serum proteins and 3 downregulated serum proteins, in samples from 50 ground crew personnel working at an air force station. Then, according to the results, we predicted that caldesmon (CALD1), myocilin (MYOC), zyxin (ZYX), creatine kinase M-type (CKM), insulin-like growth factor-binding protein 2 (IGFBP2), complement factor H-related protein 4 (CFHR4), prenylcysteine oxidase 1 (PCYOX1), heat shock cognate 71 kDa protein (HSPA8), and immunoglobulin lambda variable 3-21 (IGLV3-21) were associated with NIHL. We selected these DEPs as variables to perform logistic regression. Finally, a logistic regression model was constructed based on IGFBP2, ZYX, CKM, and CFHR4. The area under the curve was 0.894 (95% CI = 0.812 to 0.977). These findings suggested that IGFBP2, ZYX, CKM, and CFHR4 in serum are differentially expressed in NIHL patients and have the potential to be biomarkers for predicting the risk for NIHL. Further experiments in mice showed that ZYX and IGFBP2 in the cochlear were increased after noise exposure. ZYX and IGFBP2 may be involved in the occurrence and development of NIHL.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.

Mechanism of Ferroptosis and Its Role in Spinal Cord Injury.

Ferroptosis is a non-necrotic form of regulated cell death (RCD) that is primarily characterized by iron-dependent membrane lipid peroxidation and is regulated by cysteine transport, glutathione synthesis, and glutathione peroxidase 4 function as well as other proteins including ferroptosis suppressor protein 1. It has been found that ferroptosis played an important role in many diseases, such as neurodegenerative diseases and ischemia-reperfusion injury. Spinal cord injury (SCI), especially traumatic SCI, is an urgent problem worldwide due to its high morbidity and mortality, as well as the destruction of functions of the human body. Various RCDs, including ferroptosis, are found in SCI. Different from necrosis, since RCD is a form of cell death regulated by various molecular mechanisms in cells, the study of the role played by RCD in SCI will contribute to a deeper understanding of the pathophysiological process, as well as the treatment and functional recovery. The present review mainly introduces the main mechanism of ferroptosis and its role in SCI, so as to provide a new idea for further exploration.

Effects of arbuscular mycorrhizal inoculation on the phytoremediation of PAH-contaminated soil: A meta-analysis.

Inoculation with arbuscular mycorrhizal (AM) fungi can accelerate the phytoremediation process by increasing plant biomass and improving soil physicochemical and biological characteristics. However, a quantitative, data-based conclusion is yet to be derived on the roles of AM fungi in remediating soils polluted by polycyclic aromatic hydrocarbons (PAHs), and the impact factors are unclear. To address these issues, we performed a meta-analysis of 45 articles to estimate the effects of AM inoculation on the phytoremediation of soils polluted by PAHs and to examine the influence of experimental conditions on these effects. Our results showed that AM inoculation significantly decreased the residual soil PAHs concentration at all PAHs levels, and the largest effect of AM treatment was 48.5% compared to the non-mycorrhizal treatment. This should be attributed to increased plant growth and PAHs uptake, and soil biological activity in the rhizosphere induced by AM symbionts. Compared to the non-mycorrhizal treatment, the largest AM effects on the total plant biomass, root PAHs concentration, shoot PAHs concentration, soil bacterial biomass, soil catalase activity, and soil polyphenol oxidase activity were 51.7%, 565%, 53.1%, 141%, 100% and 51.9%, respectively. Although these effects on the above mentioned parameters varied with AM fungi (genus, species, and inoculation mode), soil PAHs (source, concentration, and type), plant type (dicots and monocots), and experimental conditions (experimental duration, soil sterilization and additional factors), few negative AM effects were observed. This study confirmed the feasibility of using AM fungi to enhance the phytoremediation of PAHs-contaminated soil.

Silence is golden? Relationship between silent behavior among online community members and operation performance from the perspective of personality trait.

As companies are transforming their branding, marketing, operations, and research and development (R&D) by running online communities to build their core competitive advantages in the digital era, the silent majority is still the norm in the online community and has become the focus of online community operations. Thus, it has become the core issue that why silent behavior of online community members occurs and its impact on operation performance of the online community. According to the traditional theory of organizational behavior, this study focuses on the theoretical model of the relationship between proactive personality, silent behavior of online community members (acquiescent, defensive, and prosocial silence), and operation performance of the online community, and further analyzes the impact of community identification on these relationships. Eight hundred online community members in China participated in this study. The results indicate that: (1) proactive personality has a significant negative impact on acquiescent silent and defensive silent behavior of the online community members, and a significant positive impact on prosocial silent behavior of the online community members; (2) The acquiescent silence and defensive silence have a significant negative impact on online community operation performance, whereas prosocial silence has a significant positive impact on community operation performance; (3) The acquiescent silence and defensive silence have a significant mediating effect on the relationship between proactive personality and community operation performance; (4) Online community identification has a moderating effect on the relationship between silent behavior and online community operation performance. The study proposes the mechanisms and double-edged sword effects of the silent behavior of online community members from the perspective of personality traits. On the one hand, it generalizes the research of traditional organizational silent behavior theory to the context of the online community. On the other hand, it provides reference and inspiration for the theoretical research and practical management of silent behavior of online community members.

Specific classification and new therapeutic targets for neuroendocrine prostate cancer: A patient-based, diagnostic study.

Objective: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer (PC) that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. In our investigation, there appeared to be a strong correlation between neuroendocrine differentiation prostate cancer (NEDPC) and NEPC. The objectives of this study included exploring whether NEDPC is an intermediate stage in the progression of high-risk prostate cancer (HRPC) to NEPC and identifying risk factors and new targets associated with survival in the treatment of NEPC. Methods: The selected prostate cancer patients were progressed to high-risk and characterized by neuroendocrine. We collected the clinical data and characteristics of patients with three types of cancer: the incidence of metastasis, site and time of metastasis, recurrence rate, related treatment methods, etc. The similarity and differences of the three groups were compared through experiment and database. Results: By analyzing the clinical data and immunohistochemical results, we found that there seems to be a clinical feature of neuroendocrine differentiation (NED) status in between when patients progress from PC to NEPC. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC. The metastasis-free survival curve and the immunohistochemical results are informing us that NEDPC can be a pre-state for diagnosing NEPC. Conclusion: NEPC is a late PC symptom that is frequently disregarded and has a bad prognosis. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC.