Preparation and in vitro/in vivo evaluation of uniform-sized Goserelin-loaded sustained release microspheres.

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg-1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL-1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL-1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms.

Reversible acetylation of HDAC8 regulates cell cycle.

HDAC8, a member of class I HDACs, plays a pivotal role in cell cycle regulation by deacetylating the cohesin subunit SMC3. While cyclins and CDKs are well-established cell cycle regulators, our knowledge of other regulators remains limited. Here we reveal the acetylation of K202 in HDAC8 as a key cell cycle regulator responsive to stress. K202 acetylation in HDAC8, primarily catalyzed by Tip60, restricts HDAC8 activity, leading to increased SMC3 acetylation and cell cycle arrest. Furthermore, cells expressing the mutant form of HDAC8 mimicking K202 acetylation display significant alterations in gene expression, potentially linked to changes in 3D genome structure, including enhanced chromatid loop interactions. K202 acetylation impairs cell cycle progression by disrupting the expression of cell cycle-related genes and sister chromatid cohesion, resulting in G2/M phase arrest. These findings indicate the reversible acetylation of HDAC8 as a cell cycle regulator, expanding our understanding of stress-responsive cell cycle dynamics.

Fully Integrated and High-Throughput Microfluidic System for Multiplexed Point-Of-Care Testing.

For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more comprehensive analytical techniques always rely on expensive and bulky instruments and large laboratories. Here, a fully integrated and high-throughput microfluidic system is proposed for ultra-multiple point-of-care immunoassay, termed Dac system. Specifically, the Dac system only requires a handheld portable device to automatically recycle repetitive multi-step reactions including on-demand liquid releasing, dispensing, metering, collecting, oscillatory mixing, and discharging. The Dac system performs high-precision enzyme-linked immunosorbent assays for up to 17 samples or targets simultaneously on a single chip. Furthermore, reagent consumption is only 2% compared to conventional ELISA, and microbubble-accelerated reactions shorten the assay time by more than half. As a proof of concept, the multiplexed detections are achieved by detecting at least four infection targets for two samples simultaneously on a singular chip. Furthermore, the barcode-based multi-target results can rapidly distinguish between five similar cases, allowing for accurate therapeutic interventions. Compared to bulky clinical instruments, the accuracy of clinical inflammation classification is 92.38% (n = 105), with a quantitative correlation coefficient of R2 = 0.9838, while the clinical specificity is 100% and the sensitivity is 98.93%.

The preparation of gallic acid-grafted cationic chitosan as effective salt-tolerant flocculants.

In this work, gallic acid was successfully grafted onto quaternary aminated chitosan to prepare a high efficiency cationic flocculant. The mechanism of flocculation and different influencing factors were studied in detail. The prepared flocculant only needs 60 mg L-1 to achieve a 98.7% and 94.5% removal rate on methyl blue (MB) and Congo red (CR), respectively. The high removal rate (93.2%) of a CR-MB mixed dye also confirms the universality of flocculation. In addition, kaolin as a simulated suspended solid was removed at a rate of 97% in the experiment at a dosage of 3 mg L-1. A zeta potential test showed that it worked best when the potential of the flocculation system was zero; this was because an electrostatic balance was reached between the flocculant and pollutant. Importantly, the three-functional molecules can provide more possibilities to form hydrogen bonds with water molecules, which is conducive to the stretching of flocculant molecular chains in salt water. The flocculant maintained a high stability in four different salt environments and has a positive industrial application significance. Furthermore, the flocculation experiment of the actual wastewater of the printing and dyeing plant found that the dye wastewater changed obviously from turbidity to clarification, which proved the practical application potential of the flocculant. This work provides a feasible idea for the preparation of bio-based flocculants.

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

An online survey on public awareness of drug clinical trials in inland cities of northern China.

Objective: The aims of this survey were to investigate the public awareness of drug clinical trials (DCTs) and willingness to participate the DCTs, and provide references for propaganda and science popularization of DCTs. Methods: A self-designed questionnaire named "an online survey questionnaire on public awareness of DCTs" was used to conduct an online survey from January to March 2022. The demographic characteristics and the response of participants to the awareness and willingness to participate the DCTs were collected. The factors affecting the public awareness of DCTs were analyzed by single factor and binary logistic regression analysis. Results: One thousand three hundred eighty valid questionnaires were collected, and the respondents' awareness rate of DCTs was 61.1%. Thirteen demographic characteristics including age, gender, education, occupation, work fields, household type, marital status, city type, income, medical insurance, medical expenditure, pressure to seek medical care, financial pressure, both significantly affected the qualified rate of participants' awareness of DCTs (p < 0.001) by single factor analysis. Binary logistic regression analysis indicated that education level, work fields, city type, medical insurance, and medical expenditure affected independently the participants' awareness rate of DCTs (p < 0.001). 52.9% of the participants were willing to take part in DCTs. "to promote medical progress" (54.4%) or "believe doctors" (31.1%) were the most frequent reasons for subjects participating in DCTs. Conclusion: The public awareness rate of DCTs and the willingness to participate in drug clinical were significantly affected by the demographic characteristics of subjects. Thus, targeting the needs of the public, propaganda, and science popularization of DCTs should be carried out and served public health.

Effect of partial substitution of complex phosphates with sodium bicarbonate on aggregation, conformation and gel properties of beef-pork-chicken complex myofibrillar proteins.

BACKGROUND: Complex phosphates (CP) can improve the physicochemical properties and gelation properties of myofibrillar fibrous protein (MP) in mixed meat products, but an excessive intake of phosphates over a long period of time is harmful to health. The present study investigated the effects of partial or complete substitution of CP with sodium bicarbonate (SB) on the physicochemical properties and gel properties of beef-pork-chicken mixed myofibrillar protein (BPC-MP), aiming to evaluate the feasibility of this method in reducing the amount of phosphate in mixed meat products. RESULTS: Under the optimal substitution conditions, the turbidity of BPC-MP was reduced by 37.8%, the net negative potential was increased by 28.9% and the modulus of elasticity (G') was increased. The tertiary structure indexes of protein (including fluorescence intensity, surface hydrophobicity and active thiol content) were significantly changed, whereas the α-helix and ß-turn angle contents in the secondary structure of protein were significantly increased. In addition, the water retention ability and strength of gel were also improved, which were increased by 20.7% and 42.6%, respectively. The results of scanning electron microscopy showed that the SB substitution group had a more compact and ordered microstructure. CONCLUSION: The results showed that partial substitution of CP with SB reduced the amount of phosphate added to BPC-MP and had a positive effect on the physicochemical and gel properties of BPC-MP. © 2024 Society of Chemical Industry.

Association between insulin resistance, metabolic syndrome and its components and lung cancer: a systematic review and meta-analysis.

BACKGROUND: A growing body of evidence points to the association between insulin resistance (IR), metabolic syndrome (MetS) and its components and lung cancer incidence, but remains controversial and unknown. METHODS: A systematic search was conducted through PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) and Wanfang databases for the corresponding studies. Each study reported the risk estimate and 95% confidence intervals (CI) for lung cancer, and a fixed effects model or random effects model was used for outcome. RESULTS: We included 31 publications involving 6,589,383 people with 62,246 cases of lung cancer. Diabetes mellitus (DM) (RR = 1.11, 95% CI 1.06-1.16, P = 0.000) and IR (RR = 2.35, 95% CI 1.55-3.58, P = 0.000) showed a positive association with lung cancer risk. BMI (RR = 0.66, 95% CI 0.54-0.81, P = 0.000) and HDL-C (RR = 0.88, 95% CI 0.79-0.97, P = 0.010) were negatively correlated with lung cancer. MetS(RR = 0.99, 95% CI 0.90-1.09, P = 0.801), TC (RR = 0.93, 95% CI 0.81-1.06, P = 0.274), TG (RR = 0.99, 95% CI 0.88-1.12,P = 0.884), LDL-C (RR = 1.01, 95% CI 0.87-1.16, P = 0.928), hypertension (RR = 1.01, 95% CI 0.88-1.15, P = 0.928), FBG (RR = 1.02, 95% CI 0.92-1.13, P = 0.677) and obesity (RR = 1.11, 95% CI 0.92-1.35, P = 0.280) were not associated with lung cancer. CONCLUSION: Our study showed that the risk of lung cancer is correlated with DM, IR, BMI, and HDL-C. Timely control of these metabolic disorders may have a positive effect on preventing lung cancer. Trial registration Our study has been registered in the Prospective Register of Systematic Reviews (PROSPERO), ID: CRD42023390710.

Particle sizes crucially affected the release of additives from tire wear particles during UV irradiation and mechanical abrasion.

In the environment, tire wear particles (TWPs) could release various additives to induce potential risk, while the effects of particle size on the additive release behavior and ecological risk from TWPs remain unknown. This study investigated the effects and mechanisms of particle sizes (>2 mm, 0.71-1 mm, and <0.1 mm) on the release behavior of TWPs additives under mechanical abrasion and UV irradiation in water. Compared to mechanical abrasion, UV irradiation significantly increased the level of additives released from TWPs. Especially, the additive releasing characteristics were critically affected by the particle sizes of TWPs, manifested as the higher release in the smaller-size ones. After 60 d of UV irradiation, the concentration of antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) reached 10.79 mg/L in the leachate of small-sized TWPs, 2.78 and 5.36 times higher than that of medium-sized and large-sized TWPs. The leachate of the small-sized TWPs also showed higher cytotoxicity. •OH and O2•- were identified as the main reactive oxygen species (ROS), which exhibited higher concentrations and dramatic attack on small-sized TWPs to cause pronounced fragmentation and oxidation, finally inducing the higher release of additives. This paper sheds light on the crucial effects and mechanism of particle sizes in the release behavior of TWPs additives, provides useful information to assess the ecological risk of TWPs.

Consumption of Apigenin Prevents Radiation-induced Gut Dysbiosis in Male C57BL/6J Mice Exposed to Silicon Ions.

The search for medical treatments to prevent radiation-induced damage to gastrointestinal tissue is crucial as such injuries can be fatal. This study aimed to investigate the effects of apigenin (AP) on the gut microbiome of irradiated mice, as it is a promising radiation countermeasure. Male C57BL/6J mice were divided into four groups, with six mice in each group. Two groups were given food with apigenin (20 mg/kg body weight or AP 20) before and after exposure to 0 or 50 cGy of silicon (28Si) ions, while another two groups of mice received regular diet without apigenin (0 mg/kg body weight or AP 0) before and after irradiation. The duodenum, the primary site for oral AP absorption, was collected from each mouse seven days after radiation exposure. Using 16S rRNA amplicon sequencing, we found significant differences in microbial diversity among groups. Firmicutes and Bacteroidetes were the major phyla for all groups, while actinobacterial and proteobacterial sequences represented only a small percentage. Mice not given dietary apigenin had a higher Firmicutes and Bacteroidetes (F/B) ratio and an imbalanced duodenal microbiota after exposure to radiation, while irradiated mice given apigenin had maintained homeostasis of the microbiota. Additionally, irradiated mice not given apigenin had decreased probiotic bacteria abundance and increased inflammation, while apigenin-supplemented mice had reduced inflammation and restored normal histological structure. In conclusion, our results demonstrate the potential of dietary apigenin as a countermeasure against radiation-induced gut injuries due to its anti-inflammatory activity, reduction of gut microbiota dysbiosis, and increase in probiotic bacteria (e.g., Lachnospiraceae, Muribaculaceae and Bifidobacteriaceae).

Does invasive acupuncture improve postoperative ileus after colorectal cancer surgery? A systematic review and meta-analysis.

Background: Postoperative ileus (POI) is one of the main complications after colorectal cancer (CRC) surgery, and there is still a lack of effective treatment. At present, the evidence for improvement of POI by invasive acupuncture (manual acupuncture and electroacupuncture, IA) is limited. This meta-analysis of randomized controlled trials (RCTs) aims to systematically review and evaluate the effect of IA in improving POI after CRC surgery. Methods: This meta-analysis was reported according to PRISMA statement and AMSTAR guidelines. The retrieval time was from the inception to February 2023. The RCTs were screened by searching the databases (PubMed, Ovid, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Database, Sinomed Database, and WANFANG). Two independent investigators screened and extracted the data, assessed the risk of bias, and performed statistical analysis. The statistical analysis was carried out by RevMan5.3. The PROSPERO International Prospective Register of Systematic Reviews received this research for registration (CRD42023387700). Results: Thirteen studies with 795 patients were included. In the primary outcome indicators: the IA group had shorter time to the first flauts [stand mean difference (SMD), -0.57; 95% CI, -0.73 to -0.41, p < 0.00001], shorter time to the first defecation [mean difference (MD), -4.92 h, 95% CI -8.10 to -1.74 h, p = 0.002] than the blank/sham stimulation (B/S) group. In the secondary outcome indicators: the IA group had shorter time to the first bowel motion (MD, -6.62 h, 95% CI -8.73 to -4.50 h, p < 0.00001), shorter length of hospital (SMD, -0.40, 95% CI -0.60 to -0.21, p < 0.0001) than the B/S group. In terms of the subgroup analysis: IA associated with enhanced recovery after surgery (ERAS) group had shorter time to the first flauts (MD, -6.41 h, 95% CI -9.34 to -3.49 h, p < 0.0001), shorter time to the first defacation (MD, -6.02 h, 95% CI -9.28 to -2.77 h, p = 0.0003) than ERAS group. Conclusion: Invasive acupuncture (IA) after CRC surgery, acupuncture or electricacupuncture with a fixed number of times and duration at therapeutic acupoints, can promote the recovery of POI. IA combined with ERAS is better than simple ERAS in improving POI. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=387700, identifier CRD42023387700.

Long-term aspirin administration suppresses inflammation in diabetic cystopathy.

Diabetic cystopathy (DCP) is one of the most common and troublesome urologic complications of diabetes mellitus, characterized by chronic low-grade inflammatory response. However, the correlation between inflammation and disease progression remains ambiguous and effective drugs interventions remain deficient. Herein, during 12-week study, 48 male Sprague-Dawley rats were randomly assigned to four groups: negative control (NC), NC treated with aspirin (NC+Aspirin), DCP, and DCP treated with aspirin (DCP+Aspirin). Type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin (65 mg/kg). After 2 weeks modeling, the rats in treatment groups received daily oral aspirin (100 mg/kg/d). After 10 weeks of treatment, aspirin ameliorated pathological weight loss and bladder weight increase in diabetic rats, accompanied by a 16.5% decrease in blood glucose concentrations. H&E, Masson, immunohistochemistry and transmission electron microscopy revealed that a dilated bladder with thickened detrusor smooth muscle (DSM) layer, inflammatory infiltration, fibrosis and ultrastructural damage were observed in diabetic rats, which were obviously ameliorated by aspirin. The dynamic investigations at 4, 7 and 10 weeks revealed inflammation gradually increased as the disease progresses. After 10 weeks of treatment, the expression of TNF-α, IL-1ß, IL-6, and NF-κB has been decreased to 78%, 39.7%, 44.1%, 33.3% at mRNA level and 67.6%, 76.7%, 71.4%, 67.1% at protein level, respectively (DCP+Aspirin vs. DCP, p < 0.01). Aspirin partially restored the increased expression of inflammatory mediators in bladder DSM of diabetic rats. The study provided insight into long-term medication therapies, indicating that aspirin might serve as a potential strategy for DCP treatment.

Microplastics exhibit lower carrying effects on the bioaccessibility and cytotoxicity of lead than montmorillonite clay particles.

Microplastics (MPs) in the environment are always colonized by microbes, which may have implications for carrying effect of pollutants and exposure risk in organisms. We present the crucial impacts and mechanisms of microbial colonization on the bioaccessibility and toxicity of Pb(II) loaded in disposable box-derived polypropylene (PP) and polystyrene (PS) MPs and montmorillonite (MMT) clay particles. After 45 d incubation, higher biomass measured by crystal violet staining were detected in MMT (1.23) than in PP and PS (0.400 and 0.721) indicating preferential colonization of microbes in clay particles. Microbial colonization further enhanced the sorption ability toward Pb(II), but inhibited the desorption and bioaccessibility of enriched Pb(II) in zebrafish and decreased the toxicity to gastric epithelial cells in an order of MMT > PS ≈ PP. The crucial effects were mainly because microbe-colonized substrates possessed higher oxygen functional groups and specific surface area and exhibited stronger interactions with Pb(II) and digestive component (i.e., pepsin) than pure substrates. This decreased the available soluble pepsin for complexing with sorbed Pb(II). The findings highlight the role of microbial colonization in modulating the exposure risks of artificial and natural substrate-associated pollutants and suggest that the risks of MPs may be overestimated compared to clay particles.

COVID-19 lockdown stress and problematic social networking sites use among quarantined college students in China: A chain mediation model based on the stressor-strain-outcome framework.

The COVID-19 pandemic has coincided with a global increase in problematic social networking sites use (PSNSU). By drawing on transactional stress theory and applying the stressor-strain-outcome (SSO) framework, we proposed and verified a chain mediation model to explore the mediating roles of fear of missing out (FoMO) and future anxiety (FA) in the relationship between COVID-19 lockdown stress (CL stress) and PSNSU. Our sample of 670 quarantined college students in China responded to a COVID-19 student stress questionnaire, a social network addiction scale, a fear of missing out scale, and a dark future scale. The results revealed that (1) CL stress significantly positively predicted PSNSU, (2) both FoMO and FA mediated the relationship between CL stress and PSNSU, (3) FoMO significantly positively predicted FA, and (4) a full chain mediation was observed between CL stress and PSNSU.

Pancancer Analysis Revealed the Value of RAC2 in Immunotherapy and Cancer Stem Cell.

Objective: To investigate the oncogenic effect and clinical significance of RAC2 in pancarcinoma from the perspective of tumor immunity and cancer stem cell. Methods: After in-depth mining of TCGA, GEO, UCSC, and other databases, basic information of the RAC2 gene and its expression in tumor tissues as well as the relationship between RAC2 and tumor were analyzed based on survival, mutation, immune microenvironment, tumor stemness, and enrichment analysis on related pathways. Results: RAC2 mRNA expression was increased in most tumor tissues and was associated with their prognosis. Compared to normal tissues, the RAC2 mutation rate was higher in patients with skin melanoma, uterine sarcoma, and endometrial cancer. RAC2 had a strong relation with immune cell infiltration, immunomodulators, immunotherapy markers, cancer stem cell of THYM, and immune-related pathways. Conclusions: This study explored the potential importance of RAC2 in the prognosis, immunotherapy, and cancer stem cell of 33 cancers, laying the foundation for mechanistic experiments and its future application in clinical practice. However, the results using bioinformatics methods could be affected by the differences in patients across databases. Thus, the present results were preliminary and required further experimental validation.

Language experience predicts music processing in a half-million speakers of fifty-four languages.

Tonal languages differ from other languages in their use of pitch (tones) to distinguish words. Lifelong experience speaking and hearing tonal languages has been argued to shape auditory processing in ways that generalize beyond the perception of linguistic pitch to the perception of pitch in other domains like music. We conducted a meta-analysis of prior studies testing this idea, finding moderate evidence supporting it. But prior studies were limited by mostly small sample sizes representing a small number of languages and countries, making it challenging to disentangle the effects of linguistic experience from variability in music training, cultural differences, and other potential confounds. To address these issues, we used web-based citizen science to assess music perception skill on a global scale in 34,034 native speakers of 19 tonal languages (e.g., Mandarin, Yoruba). We compared their performance to 459,066 native speakers of other languages, including 6 pitch-accented (e.g., Japanese) and 29 non-tonal languages (e.g., Hungarian). Whether or not participants had taken music lessons, native speakers of all 19 tonal languages had an improved ability to discriminate musical melodies on average, relative to speakers of non-tonal languages. But this improvement came with a trade-off: tonal language speakers were also worse at processing the musical beat. The results, which held across native speakers of many diverse languages and were robust to geographic and demographic variation, demonstrate that linguistic experience shapes music perception, with implications for relations between music, language, and culture in the human mind.

Minimally invasive nephrolithotomy versus retrograde intrarenal surgery in surgical management of Lower calyceal stones: a systematic review with meta-analysis.

OBJECTIVE: The efficacy and safety of minimally invasive nephrolithotomy (MPCNL) versus retrograde intrarenal surgery (RIRS) was assessed for lower calyceal (LC) stones. METHODS: Our team conducted a systematic literature search up to December, 2022, using PUBMED, EMBASE and the Cochrane Library. The study was registered in PROSPERO, CRD 42021247197. Randomized controlled trials evaluating the efficacy and safety of MPCNL versus RIRS for LC stones were collected. Heterogeneity among the studies was assessed using the χ 2 test based on the Q and I2 tests. Pooled effect sizes were calculated using a fixed model if I2 is less than 50%; otherwise, a random-effects model was chosen. The primary outcomes were the 3-month stone-free rate (3SFR) and total complications, while the secondary outcomes were the operating time, hospital stay, haemoglobin reduction, bleeding, postoperative fever and complications with the Clavien-Dindo system. A subgroup analysis of 10-20 mm LC stones was also designed. RESULTS: A total of 7 peer-reviewed trials comprising 711 patients were identified. No statistical differences were observed in the heterogeneity results of the 3SFR or total complications ( P >0.1, I2 < 50%). Compared with RIRS, MPCNL had an unfavourable safety profile, resulting in total complications [odds ratio (OR): 1.87 (95% CI: 1.05, 3.33); P =0.03], haemoglobin reduction [OR: 0.81 (95% CI: 0.15, 1.47); P =0.02] and complications with Grade I [OR: 5.52 (95% CI: 1.34, 22.83); P =0.02] but an improved efficacy and 3SFR [OR: 2.43 (95% CI: 1.48, 3.97); P =0.0004]. As for the 10-20 mm LC stones, compared with RIRS, MPCNL also had an unfavourable safety profile, resulting in total complications [OR: 2.47 (95% CI: 1.20, 5.07); P =0.01], complications with Grade I [OR: 4.97 (95% CI: 0.99, 25.01); P =0.05] and an increased hospital stay [OR: 2.46 (95% CI: 2.26, 2.66); P =0.00001] but an improved efficacy and 3SFR {OR: 3.10 (95% CI: 1.61, 5.99); P =0.0008]. The efficacy effect of MPCNL and safety effect of RIRS were nearly equal for both stones sized less than 20 mm (number needed to treat = 17, number needed to harm = 20) and stones sized 10-20 mm (number needed to treat = 20, number needed to harm = 13). No statistical difference was found between the MPCNL and RIRS groups for the rest of outcomes. CONCLUSION: Both MPCNL and RIRS are safe and effective management methods. Moreover, compared with RIRS, MPCNL had an unfavourable safety profile but improved efficacy for LC stones of ≤20 mm or 10-20 mm, and the differences were statistically significant. The relative profit of efficacy of MPCNL was similar to the relative profit of safety of RIRS.

A luminal intermediate cell state maintains long-term prostate homeostasis and contributes to tumorigenesis.

Cellular heterogeneity poses tremendous challenges for developing cell-targeted therapies and biomarkers of clinically significant prostate cancer. The origins of this heterogeneity within normal adult and aging tissue remain unknown, leaving cellular states and transcriptional programs that allow expansions of malignant clones unidentified. To define cell states that contribute to early cancer development, we performed clonal analyses and single cell transcriptomics of normal prostate from genetically-engineered mouse models. We uncovered a luminal transcriptional state with a unique "basal-like" Wnt/p63 signaling ( luminal intermediate , LumI) which contributes to the maintenance of long-term prostate homeostasis. Moreover, LumI cells greatly expand during early stages of tumorigenesis in several mouse models of prostate cancer. Genetic ablation of p63 in vivo in luminal cells reduced the formation of aggressive clones in mouse prostate tumor models. Finally, the LumI cells and Wnt signaling appear to significantly increase in human aging prostate and prostate cancer samples, highlighting the importance of this hybrid cell state for human pathologies with potential translational impact.

Efficacy and safety of the surgical treatments for lower calyceal stones: a systematic review and network meta-analysis.

OBJECTIVE: Efficacy and safety of five common surgical treatments for lower calyceal (LC) stones were assessed for LC stones 20 mm or less. METHODS: A systematic literature search was conducted up to June 2020 using PubMed, EMBASE, and Cochrane Library. The study has been registered in PROSPERO, CRD42021228404. Randomized controlled trials evaluating the efficacy and safety of five common surgical treatments for LC stones were collected, including percutaneous nephrolithotomy (PCNL), mini-PCNL (MPCNL), ultramini-PCNL (UMPCNL), extracorporeal shock wave lithotripsy (ESWL), and retrograde intrarenal surgery (RIRS). Heterogeneity among studies was assessed by using global inconsistency and local inconsistency. Both pooled odds ratio, along with 95% credible interval (CI) and the surface under the cumulative ranking curve values were calculated to assess the outcomes, paired comparisons of efficacy and safety of five treatments. RESULTS: Nine peer-reviewed randomized controlled trials, comprising 1674 patients in recent 10 years, were included. Heterogeneity tests showed no statistical significance, and a consistency model was chosen, respectively. The order of surface under the cumulative ranking curve values for efficacy was as follows: PCNL (79.4), MPCNL (75.2), UMPCNL (66.3), RIRS (29), and eSWL (0). For safety: eSWL (84.2), UMPCNL (82.2), RIRS (52.9), MPCNL (16.6), and PCNL (14.1). CONCLUSION: In the current study, all five treatments are both effective and safe. Many factors must be considered to choose surgical treatments for LC stones 20 mm or less; the results that we separate conventional PCNL into PCNL, MPCNL, and UMPCNL make the questions even more controversial. However, relative judgments are still needed to be used as reference data in clinical management. For efficacy, PCNL>MPCNL>UMPCNL>RIRS>ESWL, ESWL is statistically inferior to the other four treatments, respectively. RIRS is statistically inferior to PCNL and MPCNL, respectively. For safety, ESWL>UMPCNL>RIRS>MPCNL>PCNL, ESWL is statistically superior to RIRS, MPCNL, and PCNL, respectively. RIRS is statistically superior to PCNL. We cannot reach conclusions about which surgical treatment is the best choice for all patients with LC stones 20 mm or less; therefore, tailored treatments based on individual patients still demand more attention than ever before for both patients and urologists.

Countermeasure efficacy of apigenin for silicon-ion-induced early damage in blood and bone marrow of exposed C57BL/6J mice.

We investigated the countermeasure efficacy of apigenin (AP), given as a diet supplement, for radiation-induced damage in the hematopoietic tissues collected on day 7 after a total-body exposure of male C57BL/6J mice to 0 or 0.5 Gy of 260 MeV/n silicon (28Si) ions. We gave food with AP at the concentration of 20 mg/kg body weight (bw) (AP20) or without AP (AP0) to mice before and after irradiation. There were four groups of mice (six mice in each): Group 1- Control, i.e. No Radiation (0 Gy) with AP0; Group 2 - Radiation (0.5 Gy) with AP0; Group 3 - No Radiation (0 Gy) with AP20; and Group 4 - Radiation (0.5 Gy) with AP20. The complete blood count (CBC) and differential blood count were performed for each mouse. In the same mouse, an anti-clastogenic activity of AP was evaluated using the in vivo blood-erythrocyte micronucleus (MN) assay. Further in each mouse, bone marrow (BM) cells were collected and used for measuring the levels of activated nuclear factor-kappa B (NF-κB), and pro-inflammatory cytokines (i.e. tumor necrotic factor-alpha (TNF-α), interleukin-1α (IL-1α), IL-1 beta (IL-1ß), and IL-6). We used the colony-forming unit assay (CFU-A) as a tool to study the countermeasure efficacy of AP against the harmful effects of 28Si ions on the proliferation of the hematopoietic stem/progenitor cells (HSPCs). Our results showed that AP is highly effective not only in the prevention of leukopenia and thrombocytopenia but also in the enhancement of erythropoiesis and the proliferation of HSPCs. We also observed the potent anti-clastogenic activity of AP given to mice as a diet supplement. Further, we found that AP is very effective in the suppression of activated NF-κB and pro-inflammatory cytokines, suggesting that AP given as a diet supplement protects mice from 28Si-ion-induced damage in the hematopoietic tissues of irradiated male C57BL/6J mice via its anti-inflammation activity.