Upregulation of CKS2 in immunosuppressive cells is associated with metastasis and poor prognosis in prostate cancer: a single-cell RNA-sequencing analysis.

Background: Metastasis worsens prostate cancer (PCa) prognosis, with the immunosuppressive microenvironment playing a key role in bone metastasis. This study aimed to investigate how an immunosuppressive environment promotes PCa metastasis and worsens prognosis of patients with PCa. Methods: Candidate oncogenes were identified through analysis of the Gene Expression Omnibus (GEO) database. A prognostic model was developed for the purpose of identifying target genes. A single-cell RNA sequencing data from GEO database was used to analyze the localization of target genes in the tumor microenvironment. A pan-cancer analysis was conducted to study the cancer-causing potential of target genes across different types of tumors. Results: Fifty-one genes were found to be differentially expressed in bone metastasis compared to non-metastatic PCa, with CKS2 identified as the most significant gene associated with poor prognosis. CKS2 was shown to be linked to an immunosuppressive microenvironment and osteoclastic bone metastases, as shown by its negative correlation with immune cell infiltration and osteoblast-related gene expression. Moreover, CKS2 was found in immunosuppressive cells and was linked to bone metastasis in PCa. It was also overexpressed in different types of tumors, making it as an oncogenic gene. Conclusions: This research offers a new perspective on the potential utility of CKS2 as a therapeutic target for the prevention of metastatic PCa.

Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment.

Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

The safety and efficacy of Sotn ureteroscopy for renal and upper ureteral calculi: a prospective multicenter randomized controlled trial.

BACKGROUND: Sotn ureteroscopy is a new lithotripsy procedure developed on the basis of ureteroscopy and includes a rigid ureteral access sheath, standard mirror, lithotripsy mirror, and Sotn perfusion aspirator. Thus, we performed a prospective multicenter randomized controlled trial comparing the safety and efficacy of Sotn ureteroscopy in the treatment of renal and upper ureteral calculi. METHODS: In this study, 224 patients with renal and upper ureteral calculi were randomly divided equally into study and control groups from March 2018 to March 2022. All the patients were approved by the hospital ethics committee (proof number: ZF-2018-164-01 and ZF-2018-165-01) of the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and month after treatment and operation duration. The secondary outcome was postoperative complication rate. RESULTS: In total, for upper ureteral calculi, the SFR of 1 day after operation of the Sotn ureteroscopy group was significantly higher than the rigid ureteroscopy group (83.6% vs. 60%, P=0.006). Moreover, operative time (33.7±1.80 vs. 52.9±2.73 min, P<0.005) of the Sotn ureteroscopy group was significantly lower than the rigid ureteroscopy group. Additionally, the SFR of 1 day after operation and operative time for the study group (Sotn ureteroscopy combined with flexible ureteroscopy) and the control group (flexible ureteroscopy alone) were 63.2% and 36.8% (P=0.005), 65.6±4.06 and 80.3±4.91 (P=0.023), respectively. However, there were no significant differences in the SFR of 1 month after operation, success rate of ureteral access sheath placement, and postoperative complications between the two groups (P>0.05). In subgroups with stone diameters ≥1.5 cm and stone CT values ≥1000 Hounsfield units, Sotn ureteroscopy showed more advantages in terms of the SFR of 1 day after operation. Importantly, complications such as ureteral injury, sepsis, fever, and severe hematuria were not statistically different between the two groups (P>0.05). CONCLUSIONS: For renal and upper ureteral calculi, Sotn ureteroscopy has the advantage of a higher SFR of 1 day after the operation and a shorter operative time, suggesting that the Sotn ureteroscopy may have further potential applications in clinics.

Prostate Volume is A Predictor of Gleason Score Upgrading after Radical Prostatectomy in Low-Risk Prostate Cancer: A Systematic Review and Meta-analysis.

PURPOSE: The prediction of Gleason score (GS) upgrading in patients diagnosed with low-risk prostate cancer is particularly important when opting for active surveillance (AS). Thus, we aimed to explore the association between prostate volume and GS upgrading after radical prostatectomy in low-risk prostate cancer through a meta-analysis. METHODS: Multiple databases (Web of Science, MEDLINE, Embase, Scopus, and the Cochrane Library) were searched for eligible studies regarding this issue and reporting sufficient data up to May 2023. Specific search terms such as prostate cancer, radical prostatectomy, and prostate volume were used in our search strategy. Multivariable-adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Twenty studies comprising 14,823 patients who underwent radical prostatectomy matched our eligibility criteria. Moreover, GS upgrading between biopsy and surgical pathological specimens occurs in 32.2% (4,771) of cases. The results showed that smaller prostate volume is significantly associated with GS upgrading in patients with low-risk prostate cancer (OR = 1.08, 95% CI = 1.05-1.11; P < 0.001; I-square [I2] = 89.8%) from biopsy to radical prostatectomy after adjusting for confounding factors. Moreover, the results of our subgroup analyses revealed that smaller prostate volume remained a substantial risk factor of GS upgrading in the studies designed as retrospective cohorts and case-control studies performed in America, Italy, Turkey, and China. The findings are robust as indicated by sensitivity and meta-regression analyses. CONCLUSION: Smaller prostate volume predicts clinically substantial GS upgrading in patients diagnosed with lowrisk prostate cancer after radical prostatectomy. The intriguing findings might be helpful when management options other than surgery are selected based on the inability to recognise the true pathological GS of patients for AS. Further studies focus on risk-stratification and treatment planning for patients with low-grade prostate cancer are still needed to verify our results.

Icariin inhibits prostate cancer bone metastasis and destruction via suppressing TAM/CCL5-mediated osteoclastogenesis.

BACKGROUND: Bone metastasis occurs in nearly 70% of patients with metastatic prostate cancer (PCa), and represents the leading cause of death in patients with PCa. Emerging evidence has demonstrated the potential activities of icariin in modulating bone metabolism and remodelling the tumor microenvironment (TME). However, whether icariin could inhibit PCa bone metastasis and destruction by modulating the TME as well as the underlying mechanisms remains unclear. PURPOSE: This study investigated whether icariin could inhibit PCa bone metastasis and destruction by modulating the bone TME as well as the underlying mechanisms. METHODS: Osteoclasts were induced from mouse bone marrow-derived macrophages (BMMs) or Raw264.7 cells. PCa cells were cultured in the conditional medium (CM) of macrophages in vitro or co-injected with macrophages in vivo to simulate their coexistence in the TME. Multiple molecular biology experiments and the mouse RM1-Luc PCa bone metastasis model were used to explore the inhibitory activity and mechanism of icariin on PCa metastasis and bone destruction. RESULTS: Icariin treatment significantly suppressed PCa growth, bone metastasis and destruction as well as osteoclastogenesis in vivo. Furthermore, icariin remarkably inhibited osteoclast differentiation, even in the presence of the CM of tumor-associated macrophages (TAMs), while exhibiting no obvious effect on osteoblasts. Moreover, icariin suppressed the M2 phenotype polarization of Raw264.7-derived TAMs and transcriptionally attenuated their CC motif chemokine ligand 5 (CCL5) expression and secretion via inhibiting SPI1. Additionally, CCL5 induced the differentiation and chemotaxis of osteoclast precursor cells by binding with its receptor CCR5. The clinicopathological analysis further verified the positive correlation between the TAM/CCL5/CCR5 axis and osteoclastogenesis within the TME of PCa patients. More importantly, icariin remarkably suppressed PCa metastasis-induced bone destruction in vivo by inhibiting osteoclastogenesis via downregulating the TAM/CCL5 pathway. CONCLUSION: Altogether, these results not only implicate icariin as a promising candidate immunomodulator for PCa bone metastasis and destruction but also shed novel insight into targeting TAM/CCL5-mediated osteoclastogenesis as a potential treatment strategy for osteolytic bone metastasis. This study helps to advance the understanding of the crosstalk between bone TME and bone homeostasis.

System analysis identifies UBE2C as a novel oncogene target for adrenocortical carcinoma.

Ubiquitin Conjugating Enzyme 2C (UBE2C) is an emerging target gene for tumor progression. However, the tumorigenic effect and mechanism of UBE2C in adrenocortical carcinoma (ACC) remains unclear. Systematic investigation of the tumorigenic effect of UBE2C may help in understanding its prognostic value in adrenocortical carcinoma. First, we exploited the intersection on DFS-related genes, OS-related genes, highly expressed genes in adrenocortical carcinoma as well as differentially expressed genes (DEGs) between tumor and normal, and then obtained 20 candidate genes. UBE2C was identified to be the most significant DEG between tumor and normal. It is confirmed that high expression of UBE2C was strongly associated with poor prognosis in patients with ACC by analyzing RNA-seq data of ACC obtained from the Cancer Genome Atlas (TCGA) database implemented by ACLBI Web-based Tools. UBE2C expression could also promote m6A modification and stemness in ACC. We found that UBE2C expression is positively associated with the expression of CDC20, CDK1, and CCNA2 using ACLBI Web-based Tools, indicated the hyperactive cell cycle progression present in ACC with high UBE2C expression. In addition, UBE2C knockdown could significantly inhibit the proliferation, migration, invasion, EMT of adrenocortical carcinoma cells as well as the cell cycle progression in vitro. Notably, pan-cancer analysis also identified UBE2C as an oncogene in various tumors. Taken together, UBE2C was strongly associated with poor prognosis of patients with ACC by promoting cell cycle progression and EMT. This study provides a new theoretical basis for the development of UBE2C as a molecular target for the treatment of ACC.

Zn2+ regulates human oxalate metabolism by manipulating oxalate decarboxylase to treat calcium oxalate stones.

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mostly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that zinc gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in humans through clinical experiments on patients also subjected to antibiotic treatment. The analysis of clinical samples revealed that an imbalance of Lactobacillus and oxalate decarboxylase (OxDC) was involved in the formation of CaOx kidney stones. Then, we identified that Zn2+ could be used as an external factor to improve the activity of OxDC and promote Lactobacillus in the intestinal flora, and this treatment achieved a therapeutic effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and completing in vitro experiments, we propose a model of the Zn2+-induced reduction of CaOx kidney stone symptoms in rats by increasing the metabolism of oxalate through the positive effects of Zn2+ on Lactobacillus and OxDC.

A novel alternative strategy for monitoring and insight into liver fibrosis progression: The combination of surface-enhanced Raman spectroscopy (SERS) and gut microbiota.

Nowadays, the studies on the interaction and relationship between the intestinal microorganisms and liver diseases are increasing. However, it is still a huge challenge for the in-depth investigation and dynamic monitoring of such a complex network. Herein, a significant discovery was made. A strong association between gut microbial structural and functional genomics and SERS spectra of hepatocytes were revealed. Based on the study of gut microbes and SERS spectra, complementary information could be provided for the mechanism analysis of related diseases. Liver fibrosis, a chronic liver disease that lack specific cure was thus comprehensive studied. Liver targeting gold nanoparticle dimers were prepared as the SERS tags, and abundant SERS peak signals were acquired. Meanwhile, the gut microbiomes were also comparative studied. The changes of carbohydrates and lipids in liver cells were observed at the early stages of liver fibrosis, and TLR4 (toll-like receptors 4) was activated to elicit immune responses. Then again, oxidative stress, endotoxin and serum inflammatory factors were the major observations at the late stages. The SERS signals and the microbiome analysis were well confirmed and complemented each other, which suggested that the detection strategy could be another valuable method for the "gut-liver axis" study.

Formation of pre-metastatic bone niche in prostate cancer and regulation of traditional chinese medicine.

Prostate cancer with bone metastasis has a high cancer-specific mortality. Thus, it is essential to delineate the mechanism of bone metastasis. Pre-metastatic niche (PMN) is a concept in tumor metastasis, which is characterized by tumor-secreted factors, reprogramming of stromal cells, and immunosuppression by myeloid-derived suppressor cells (MDSC), which is induced by bone marrow-derived cells (BMDC) in the target organ. However, PMN does not explain the predilection of prostate cancer towards bone metastasis. In this review, we discuss the initiation of bone metastasis of prostate cancer from the perspective of PMN and tumor microenvironment in a step-wise manner. Furthermore, we present a new concept called pre-metastatic bone niche, featuring inherent BMDC, to interpret bone metastasis. Moreover, we illustrate the regulation of traditional Chinese medicine on PMN.

Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Zoledronic acid (ZA) does not improve the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC); however, little is known about the efficacy of ZA in to hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non- metastatic castration-resistant prostate cancer (nmCRPC). Therefore, we assessed the efficacy of ZA in patients with prostate cancer (PCa) and different disease statuses. METHODS: Fifteen eligible randomized-control trials (RCTs) with ZA intervention, including 8280 participants with HSPC, mHSPC, nmCRPC, and mCRPC, were analyzed. The primary and secondary outcome were overall survival(OS), and skeletal-related events (SREs), and bone mineral density (BMD). RESULTS: The participants included 8280 men (7856 non-Asian and 424 Asian). Seven trials yielded a pooled hazard ratio (HR) of 0.95 (0.88, 1.03; P = 0.19) for OS. Subgroup analysis revealed no significant improvement in OS in the HSPC, castration-resistant prostate cancer (CRPC), M0 and M1(bone metastasis) groups, with pooled HR (95%CI) of 0.96 (0.88,1.05), 0.78 (0.46,1.33), 0.95 (0.81,1.13), 0.85 (0.69,1.04) respectively. The Asian group exhibited improved in OS with an HR of 0.67 (0.48, 0.95; P = 0.02), whereas the non-Asian group showed no improvement in OS with an HR of 0.97 (0.90, 1.06; P = 0.52). Five trials yielded pooled odds ratio (OR) of 0.65 (0.45, 0.95; P = 0.02) for SREs. In the subgroup, SREs were significantly decreased in the M1 and Asian groups with ORs of 0.65 (0.45, 0.95; P = 0.02) and 0.42 (0.24, 0.71; P = 0.001), respectively. Six trials yielded a pooled mean difference (MD) of 8.08 (5.79, 10.37; P < 0.001) for BMD. In the HSPC we observed a stable improvement in increased BMD percentage with an MD (95%CI) of 6.65 (5.67, 7.62) (P = 0.001). CONCLUSIONS: ZA intervention does not significantly improve OS in patients with prostate cancer (HSPC, CRPC, M0, M1) but probably improves OS in the Asian populations. M1 and Asian groups had exhibit a significant reduction in SREs regardless of the HSPC or CRPC status after ZA administration. Moreover, ZA treatment increases BMD percentage.

Dynamic monitoring of bacteriostatic process by SERS analysis based on a simple but effective detection strategy.

Investigating antibacterial process at a molecular level is helpful to fully understand the mechanism of bacteriostasis and develop new antimicrobial agents. Herein, a simple but effective sensor strategy of antibacterial nanocomposite combined with surface-enhanced Raman scattering (SERS) substrate was applied for the robust detection of bacteriostatic process. The synergistic SERS effect of nanocomposite and Ag nanoparticles (NPs) substrate was confirmed by finite difference time domain (FDTD) solutions. A curcumin liposome@Au NPs nanocomposite was designed and prepared as a kind of bacteriostatic agent and SERS material as well. By means of electrostatic attraction between the nanocomposite and bacteria (methicillin resistant staphylococcus aureus, MRSA), specific detection of MRSA and monitoring of the molecular structure changes after bacteriostaticeffect were realized by SERS. Important intermediates produced in the bacteriostatic process were also measured at the same time. The relationship between the relative peak intensities and the structure of MRSA were thus established. The results were verified by high performance liquid chromatography-mass spectrometry (HPLC-MS), reactive oxygen species (ROS) kit, and flow cytometry. The detection strategy we proposed could not only be used for real-time detection of bacteriostatic processes with a high efficiency, but also a powerful tool for analyzing the mechanism in biochemical processes.

Low serum total testosterone level as a predictor of upgrading in low-risk prostate cancer patients after radical prostatectomy: A systematic review and meta-analysis.

PURPOSE: To investigated the association between serum total testosterone and Gleason score upgrading of low-risk prostate cancer after radical prostatectomy (RP). MATERIALS AND METHODS: Medline, Web of Science, Embase, and Cochrane Library databases were searched to identify eligible studies published before October 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random or fixed effects models. RESULTS: Five studies comprising 1,203 low-risk prostate cancer patients were included. The results showed that low serum total testosterone (<300 ng/dL) is associated with a high rate of Gleason score upgrading after RP (OR, 2.3; 95% CI, 1.38-3.83; p<0.001; I², 92.2%). Notably, sensitivity and meta-regression analyses further strengthen the reliability of our results. CONCLUSIONS: Our results support the idea that low serum total testosterone is associated with a high rate of Gleason score upgrading in prostate cancer patients after RP. It is beneficial for urologist to ensure close monitoring of prostate-specific antigen levels and imaging examination when choosing non-RP treatment for low-risk prostate cancer patients.

Immunoglobulin G4-related kidney disease involving the renal pelvis and perirenal fat: A case report.

BACKGROUND: Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an autoimmune disease associated with chronic and progressive inflammation and fibrosis. It is difficult to differentiate IgG4-RD involving the kidney from infectious diseases and malignancy on imaging. CASE SUMMARY: We report the case of a 51-year-old Chinese man whose abdominal computed tomography scan showed diffuse bilateral enlargement of the kidneys and perirenal fat, thickening of the renal pelvic walls, and hydronephrosis of the right kidney. Relevant laboratory test results showed a serum creatinine level of 464 µmol/L. The patient was diagnosed with acute renal failure and was started on intermittent hemodialysis. Further tests revealed high serum IgG4 levels (20.8 g/L) and an enlarged right submaxillary lymph node. Biopsy and histopathological examination of the enlarged node led to the diagnosis of IgG4-RD. After corticosteroid therapy, his serum creatinine level quickly decreased to near normal levels. CONCLUSION: IgG4-RD affecting the renal pelvis or perirenal fat is rare, with atypical imaging features. Multidisciplinary consultation is critical for accurate diagnosis and treatment of this disease. Suspected cases should undergo biopsy to avoid misdiagnosis.

Prevalence and risk factors for incidental prostate cancer in patients after transurethral resection of the prostate with negative results on prostate biopsy: A retrospective study.

PURPOSE: This study aimed to explore the prevalence and predictors of incidental prostate cancer (IPC) after transurethral resection of the prostate (TURP) with negative results on transperineal magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS) fusion prostate biopsy or TRUS-guided prostate biopsy. MATERIALS AND METHODS: Data of 253 patients who underwent TURP with a preliminary diagnosis of benign prostatic hyperplasia (BPH) were evaluated. The prevalence of IPC was calculated. Univariate and multivariate logistic regression analyses were conducted to explore independent predictive factors of IPC. RESULTS: A total of 253 patients were included. IPC was diagnosed in 12 patients (4.7%). The mean age of the patients and the mean prostate volume were 69.8±7.07 years and 89.3±49.29 mL, respectively. The prevalence of IPC was higher in the TRUS guided prostate biopsy group than in the transperineal MRI/TRUS fusion prostate biopsy group (11 of 203 [5.4%] vs. 1 of 50 [2.0%], p=0.47), but the difference was not statistically significant. Our results indicated that older age (≥70 y) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.02-1.27; p=0.025) and smaller prostate volume (OR, 0.97; 95% CI, 0.938-0.998; p=0.039) were associated with an increased incidence of IPC after TURP. CONCLUSIONS: Our findings indicate that the prevalence of IPC may be higher among patients who undergo transrectal prostate biopsy before TURP than among those who undergo transperineal MRI/TRUS fusion prostate biopsy. Older age and smaller prostate volume were independent predictors of increasing the risk for IPC after TURP.

Comparisons of efficacy and complications between transrectal and transperineal prostate biopsy with or without antibiotic prophylaxis.

BACKGROUND AND PURPOSE: We aimed to determine the cancer detection rate and complications of transrectal prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in the hospital. However, given the use of antibiotic prophylaxis in TPBx remains controversial according to the current guidelines, we also investigated the safety and side effects of TPBx with and without antibiotic prophylaxis. MATERIALS AND METHODS: A total of 777 patients who underwent prostate biopsy were enrolled in this study in accordance with the criteria. The primary outcome was pooled infectious complications (sepsis, fever, symptomatic urinary tract infection and urinary retention), and the secondary outcome was prostate cancer detection rate. RESULTS: Findings showed that TPBx and TRBx were equivalent in terms of prostate cancer detection rate (TPBx: 50.4% vs. TRBx: 47.3%; P = 0.424) and urinary retention (TPBx: 5% vs. TRBx: 6.3%; P = 0.451). However, TRBx had significantly higher incidences of sepsis (risk ratios, RR: 3.65, 95% confidence interval [CI]: 1.21-11.03; P = 0.014) and symptomatic urinary tract infection (RR: 3.04, 95% CI: 1.07-8.66; P = 0.029) than TPBx. Notably, for TPBx, patients who received a single dose of cephazolin prophylaxis were not associated with the risk of sepsis (RR: 0.78, 95% CI: 0.13-4.63; P = 0.783) and symptomatic urinary tract infection (RR: 1.17, 95% CI: 0.24-5.74; P = 0.848) in contrast to patients who did not receive any antibiotic prophylaxis. Meanwhile, no effects on prostate cancer detection rate and urinary retention were observed in the TPBx group. CONCLUSIONS: Our findings indicated that TPBx significantly reduced infectious complications compared with TRBx and should therefore be preferred. Importantly, we need to re-examine whether the antibiotic prophylaxis should be routinely applied before TPBx in consideration of increasing antibiotic resistance. This result complements the current national guidelines. Nevertheless, future studies on this topic with improved quality and increased sample size are still needed to minimise bacterial resistance.

Acupressure versus parecoxib sodium in acute renal colic: A prospective cohort study.

Background: Here provides a complementary treatment, acupressure at the Qiu acupoint, a novel acupoint, which potentially alleviates renal colic. Materials and methods: 90 patients were included in this study. Acupressure-group patients (n = 46) were administered acupressure at the Qiu acupoint following a preset protocol. Parecoxib sodium-group patients (n = 44) were administered parecoxib sodium (40 mg) (via the direct intravenous route). The visual analog scale (VAS) was used to evaluate pain intensity at baseline and at 1, 5, 10, 20, 30, and 120 min after initiating the intervention. Linear mixed effects model was performed to detect the rate of decrease of VAS per time and their covariant effect on the efficacy of acupressure. Results: No significant statistical differences in baseline data and VAS scores were observed. The acupressure group obtained lower VAS scores at the 1st, 5th, 10th, and 20th minute than the parecoxib sodium group after initiating the intervention (mean: 4.33 vs. 7.61, mean difference (MD): 3.29, 95% CI: 0.23, 2.84; mean: 2.65 vs. 7.61, MD: 4.96, 95% CI: 4.44, 5.49; mean: 1.63 vs. 6.59, MD: 4.96, 95% CI: 4.48, 5.44; mean: 1.26 vs. 3.64 MD: 2.38, 95% CI: 1.87, 2.88; P < 0.05). The markedly effective rate was similar between the two groups. The linear mixed effects model demonstrated that acupressure at the Qiu point was significantly faster than parecoxib sodium in decreasing VAS scores with an estimate of -2.05 (95% CI: -2.51, -1.59, p = 0.000), especially within 10 minutes with an estimate of 0.18 (95% CI: 0.12, 0.25, p = 0.000). Conclusion: Acupressure at the Qiu acupoint is significantly faster than parecoxib sodium in decreasing VAS scores within 10 minutes. Clinical trial registration: http://www.chictr.org.cn/, identifier 2100047168.

Periodontal disease and the risk of prostate cancer: a meta-analysis of cohort studies

ABSTRACT Background: Periodontal disease is reportedly associated with the risk of various systemic diseases, including pancreatic and lung cancers. However, its association with prostate cancer remains inconclusive. Herein, we explored the association of periodontal disease with the risk of prostate cancer through a meta-analysis. Materials and Methods: MEDLINE, Embase, Web of Sciences and Cochrane Library databases were searched for eligible publications up to April 2020. Multivariate adjusted risk estimates with corresponding 95% confidence intervals (CIs) were extracted and calculated using random- or fixed-effect models. Results: Nine cohort studies involving 3.353 prostate cancer cases with 440.911 participants were identified and included in the meta-analysis. We found that periodontal disease significantly increased the risk of prostate cancer by 1.40-fold (hazard ratio [HR]=1.40, 95% CI: 1.16-1.70; P=0.001; I2=76.1%) compared with normal condition. Interestingly, the risk of developing prostate cancer was not significant in patients treated with periodontal therapy (HR=1.22, 95% CI: 0.86-1.73; P=0.272; I2=65.2%). The results of subgroup analyses were also consistent and significant when stratified by study design and follow-up period, whereas conflicting results were observed in periodontal disease ascertainment stratification. These findings were robust as indicated by sensitivity analyses. Conclusions: Periodontal disease was associated with the increased risk of prostate cancer, whereas no significant association was observed in patients treated with periodontal therapy. Hence, the awareness and importance for maintaining oral health should be improved, and the underlying mechanisms linking periodontal disease and prostate cancer should be fully explored in future research.

Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway.

The Polycomb protein enhancer of zeste homolog 2 (EZH2) has critical roles in prostate cancer (PCa) progression and drug-resistance, which remains an obstacle for PCa treatment. Enzalutamide (ENZ) is a second-generation androgen receptor antagonist employed for treatment of metastatic castration-resistant prostate cancer A considerable proportion of tumors eventually develop resistance during treatment. Thus, agents that can overcome resistance to PCa are needed urgently. Ilicicolin A (Ili-A), an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, shows antiproliferative activity in human PCa cells, but its mechanism of action against Castration-resistant prostate cancer is not known. Herein, RNA-sequencing showed the EZH2 pathway to be involved in PCa proliferation. Ili-A at low doses reduced the protein level of EZH2, leading to transcriptional change. Interestingly, Ili-A suppressed the binding of EZH2 to promoter regions in AR/serine/threonine polo-like kinase-1/aurora kinase A. Moreover, Ili-A could enhance the anticancer activity of enzalutamide in CRPC cancer models. These data suggest that Ili-A could be used in combination with enzalutamide to treat CRPC.

Cyclopentenone-Containing Tetrahydroquinoline and Geldanamycin Alkaloids from Streptomyces malaysiensis as Potential Anti-Androgens against Prostate Cancer Cells.

Malaymycin (1), a new cyclopentenone-containing tetrahydroquinoline alkaloid, and mccrearamycin E (2), a geldanamycin analogue bearing a rare ring-contracted cyclopentenone moiety, and a C2-symmetric macrodiolide (7) were isolated from Streptomyces malaysiensis SCSIO41397. Their structures including absolute configurations were determined by detailed analyses of NMR and HRMS data and ECD calculations. The occurrence of mccrearamycin E (2) bearing a ring-contracted cyclopentenone is rare in the geldanamycin class. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds 1, 4, 5, and 7 showed cytotoxicity against some or all of the five cancer cell lines with IC50 values ranging from 0.067 to 7.2 µM. In particular, compound 1 inhibited the growth of C42B and H446 cell lines with IC50 values of 67 and 70 nM, respectively. Malaymycin (1) significantly induced cell cycle arrest at the G0/G1 phase in C42B cell lines and caused cell shrinkage and inhibited the expression of the androgen receptor (AR) at both the mRNA and protein levels in a dose-dependent manner. Further examination by qRT-PCR analysis showed that 1 strongly suppressed the expression of AR target genes KLK2 and KLK3 in the C42B and 22RV1 cell lines, which suggested that 1 might be a promising potential lead compound for the development of a treatment for the castration-resistant prostate cancer (CRPC).

SERS diagnosis of liver fibrosis in the early stage based on gold nanostar liver targeting tags.

In order to realize the accurate and early diagnosis of liver fibrosis, a long slow pathological process which may lead to cirrhosis or even liver cancer, liver targeting tags made up of gold nanostars and glycyrrhetinic acid are reported in this paper. Gold nanostars (GNSs) and GNS liver targeting tags (GLTTs) were injected into model mice with stage S1 liver fibrosis and normal mice via the tail vein respectively, then the SERS spectra were collected. GLTTs had a better detection effect on liver tissue than unmodified GNSs (12.85 times), and better detection reproducibility as well. Moreover, according to the MTT and survival analysis experiments, GLTTs also had better biocompatibility. Hence, the changes of 10 SERS signals and other substances in the early stage of liver fibrosis were analyzed at the molecular level, and the SERS characteristic peaks that could be used for the diagnosis of early liver fibrosis were screened out. Revealed by the experimental results, the GLTTs designed and prepared were applicable to the efficient SERS detection of early liver fibrosis in mice, and the strategy we have proposed might be a potential approach for the early diagnosis of this disease in clinics.