Phase transition of spindle-associated protein regulate spindle apparatus assembly.

Spindle assembly required during mitosis depends on microtubule polymerization. We demonstrate that the evolutionarily conserved low-complexity protein, BuGZ, undergoes phase transition or coacervation to promote assembly of both spindles and their associated components. BuGZ forms temperature-dependent liquid droplets alone or on microtubules in physiological buffers. Coacervation in vitro or in spindle and spindle matrix depends on hydrophobic residues in BuGZ. BuGZ coacervation and its binding to microtubules and tubulin are required to promote assembly of spindle and spindle matrix in Xenopus egg extract and in mammalian cells. Since several previously identified spindle-associated components also contain low-complexity regions, we propose that coacervating proteins may be a hallmark of proteins that comprise a spindle matrix that functions to promote assembly of spindles by concentrating its building blocks.

Isolation and characterization of rabbit limbal niche cells.

Limbal niche cells (LNCs) are one of the most important supporting cells for corneal epithelial stem cells (CES), however, research on LNCs has been mostly limited to humans and rats previously. To expand the research work into the rabbit animal model, one of the most often used animals in stem cell study, this study was carried out for the in vitro isolation and identification of rabbit LNCs. Rabbit LNCs were isolated by collagenase A digestion method and single cells were obtained, the cells were then seeded on 5% Matrigel-coated plastic surface and cultured in modified embryonic stem cell medium (MESCM). Three biological replicates of the isolating and characterization were recorded from New Zealand White rabbits aged from 2.5 months to 5 months. LNC markers (VIM/CD90/CD105/SCF/PDGFRß) were analyzed using tyramide signal amplification (TSA) staining, immunohistochemical staining (IHC), western blotting (WB), and real-time reverse transcription polymerase chain reaction (qPCR). TSA staining suggested that VIM was highly expressed in rabbit limbus stroma, which was confirmed by WB, and P63α was expressed in the basal limbus epithelium. Pan-CK and CK12 were highly expressed in the central corneal epithelium but lightly expressed in the limbal epithelium. The WB result indicated that PDGFRß and VIM expressions in rabbit-LNCs P4 were higher than in P1 and P7. In addition, rabbit corneal epithelium highly expressed Paired Box 6 (PAX6) and Epidermal growth factor-like domain 6(EGFL6). For the three repeat experiments, the cell expansion activity of rabbit-LNC was highest at P4. Rabbit-LNCs were passaged from P0 to P7, and the number of cell doublings (NCD) of P4 for the three repeat experiments was 2.816, 2.737, and 2.849. qPCR showed that high mRNA expression levels of VIM, CD90, CD105, SCF, and PDGFRß in rabbit-LNCs P4. In conclusion, rabbit-LNCs could be successfully isolated by the collagenase A digestion method as used in human tissue. There were similar characteristics between rabbit and human LNCs (VIM+/CD90+/CD105+/SCF+/PAX6+/PDGFRß+).

T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

Association between drinking status and risk of kidney stones among United States adults: NHANES 2007-2018.

OBJECTIVE: This study aimed to investigate the relationship between drinking status and kidney stones occurrence among United States (US) adults who consume alcohol. METHODS: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES 2007-2018). Questionnaires yielded information on alcohol consumption and kidney health. Drinking status was categorized into four groups-former, mild, moderate, and heavy-based on alcohol consumption patterns. The aim was to explore the relationship between drinking status and the prevalence of kidney stones occurrence. For this analysis, we examined a group of individuals diagnosed with kidney stones. With survey weights applied, the total weight of the group was 185,690,415. RESULTS: We used logistic regression to measure the relationship between drinking status and the likelihood of developing kidney stones. In a fully adjusted model, former drinkers were less likely to have previously experienced kidney stones (OR 0.762, 95% CI 0.595-0.977, P < 0.05). In subgroup analysis, heavy alcohol consumption was associated with a significantly reduced likelihood of kidney stones occurrence in various populations. The adjusted odds ratios (with 95% confidence intervals) of kidney stones risk for heavy alcohol consumption were 0.745 (0.566-0.981) for young individuals, 0.566 (0.342-0.939) for older individuals, 0.708 (0.510-0.981) for individuals of white race, 0.468 (0.269-0.817) for individuals with underweight/normal BMI, 0.192 (0.066-0.560) for widowed people, 0.538 (0.343-0.843) for smoking individuals, 0.749 (0.595-0.941) for individuals without a cancer history, and 0.724 (0.566-0.925) for individuals without a stroke history. CONCLUSIONS: In US adults who consume alcohol, a negative linear relationship is apparent between drinking status and the prevalence of kidney stones, with heavy drinking showing a lower prevalence compared to former drinkers. However, the causal relationship between drinking status and kidney stones requires further investigation in future research endeavors.

Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.

Interaction between drinking and dietary inflammatory index affects prostate specific antigen: a cross-sectional study.

BACKGROUND: Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate cancer (PCa) remains controversial. Although alcohol is included in DII as a dietary factor, the various adverse health effects of alcohol consumption are not only related to inflammation. On the other hand, it has been a long-standing debate whether alcohol consumption is linked to the risk of PCa. Therefore, to clarify whether drinking affects the relationship between DII and PCa, we evaluated the correlation between DII and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: We used data from the NHANES spanning from 2005 to 2010 to analyze the relationship between PCa and DII. Out of the 31,034 NHANES participants, we enrolled 4,120 individuals in our study, utilizing dietary intake data from a twenty-four-hour period to determine DII scores. Demographic data, physical and laboratory test results were collected to compare between low PSA and high PSA groups, and to calculate the odds ratio between both groups, we employed a logistic regression analysis. RESULTS: In this cross-sectional investigation of PCa, drinkers and non-drinkers had different relationships between DII and PSA levels (OR: 1.2, 95% Cl: 1-1.44 vs. OR: 0.98, 95% Cl: 0.9-1.07), and DII and abstaining from alcohol were effective in reducing the incidence of PSA (p-value for significant interaction = 0.037). CONCLUSION: The results of our study suggest that drinking may influence the relationship between DII and PSA levels. DII is likely to be a reliable indicator for estimating PSA levels among non-drinkers, who may limit their intake of pro-inflammatory ingredients to lower the incidence and death of PCa.

GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126.

Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves and lymphovenous valves, and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of the cell junction molecules VE-cadherin and claudin 5 in lymphatic vessels. We identified miR-126 as a target of GATA2, and miR-126-/- embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (HLECΔGATA2) have altered expression of claudin 5 and VE-cadherin, and blocking miR-126 activity in HLECs phenocopies these changes in expression. Importantly, overexpression of miR-126 in HLECΔGATA2 significantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 activity and uncovers miR-126 as a novel regulator of mammalian lymphatic vascular development.

Prevalence and risk factors of incidental prostate cancer in certain surgeries for benign prostatic hyperplasia: A systematic review and meta-analysis.

BACKGROUND: This study aimed to explore the prevalence and clinical risk factors in patients diagnosed with incidental prostate cancer (IPC) during certain surgeries (transurethral resection of the prostate [TURP], open prostatectomy [OP], and holmium laser enucleation of the prostate [HoLEP]) after clinically suspected benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Literature search of the MEDILINE, Web of Science, Embase, and Cochrane Library databases was performed to identify eligible studies published before June 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) of the prevalence and clinical risk factors of IPC were calculated using random or fixed-effect models. RESULTS: Twenty-three studies were included in the meta-analysis. Amongst the 94.783 patients, IPC was detected in 24.715 (26.1%). Results showed that the chance of IPC detection (10%, 95% CI: 0.07-4.00; P<0.001; I2=97%) in patients treated with TURP is similar to that of patients treated with HoLEP (9%, 95% CI: 0.07-0.11; P<0.001; I2=81.4%). However, the pooled prevalence estimate of patients treated with OP was 11% (95% CI: -0.03-0.25; P=0.113; I2=99.1%) with no statistical significance. We observed increased incidence of IPC diagnosis after BPH surgery amongst patients with higher prostate-specific antigen (PSA) level (OR: 1.13, 95% CI: 1.04-1.23; P=0.004; I2=89%), whereas no effect of age (OR: 1.02, 95% CI: 0.97-1.06; P=0.48; I2=78.8%) and prostate volume (OR: 0.99, 95% CI: 0.96-1.03; P=0.686; I2=80.5%) were observed. CONCLUSIONS: The prevalence of IPC was similar amongst patients undergoing TURP, HoLEP, and OP for presumed BPH. Interestingly, increased PSA level was the only independent predictor of increasing risk of IPC after BPH surgery rather than age and prostate volume. Hence, future research should focus on predictors which accurately foretell the progression of prostate cancer to determine the optimal treatment for managing patients with IPC after BPH surgery.

Circular drought-hardening confers drought tolerance via modulation of the antioxidant defense system, osmoregulation, and gene expression in tobacco.

Drought stress hinders the growth and development of crop plants and ultimately its productivity. It is expected that drought stress will be frequent and intense in the future due to drastic changes in the global climate. It is necessary to make crop plants more resilient to drought stress through various techniques; drought-hardening is one of them. Defining various metabolic strategies used by tobacco plants to confer drought tolerance will be important for maintaining plant physiological functions, but studies addressing this topic are limited. This study was designed to elucidate the drought tolerance and adaptation strategies used by tobacco plants via the application of different circular drought-hardening cycles (control: no drought-hardening, T1: one cycle of drought hardening, T2: two cycles of drought-hardening, and T3: three cycles of drought-hardening) to two tobacco varieties namely Honghuadajinyuan (H) and Yun Yan-100 (Y). The results revealed that drought-hardening decreased the fresh and dry biomass of the tobacco plants. The decrease was more pronounced in the T3 treatment for both H (23 and 29%, respectively) and Y (26 and 31%, respectively) under drought stress. The MDA contents, especially in T1 and T2 in both varieties, were statistically similar compared with control under drought stress. Similarly, higher POD, APX, and GR activities were observed, especially in T3, and elevated amounts of AsA and GSH were also observed among the different circular drought-hardening treatments under drought stress. Thus circular drought-hardening mitigated the oxidative damage by increasing the antioxidant enzyme activities and elevated the content of antioxidant substances, a key metabolic strategy under drought stress. Similarly, another important plant metabolic strategy is the osmotic adjustment. Different circular drought-hardening treatments improved the accumulation of proline and soluble sugars contents which contributed to osmoregulation. Finally, at the molecular level, circular drought-hardening improved the transcript levels of antioxidant enzyme-related genes (CAT, APX1, and GR2), proline and polyamines biosynthesis-related genes (P5CS1 and ADC2), and ABA signaling (SnRK2), and transcription factors (AREB1 and WRKY6) in response to drought stress. As a result, circular drought-hardening (T2 and T3 treatments) promoted tolerance to water stress via affecting the anti-oxidative capacity, osmotic adjustment, and regulation of gene expression in tobacco.

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

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.

Upregulation of lncRNA-NONRATT021203.2 in the dorsal root ganglion contributes to cancer-induced pain via CXCL9 in rats.

Cancer-induced pain (CIP) is a kind of chronic pain that occurs during cancer progression over time. However, the mechanisms are largely unknown, and clinical treatment remains challenging. LncRNAs have been reported to play critical roles in various biological processes, including chronic pain. The aim of our study was to investigate whether lncRNAs participate in the development of CIP by regulating the expression levels of some molecules related to pain modulation. The CIP model was established by injecting Walker 256 mammary gland tumor cells into the tibial canal of rats. In this study, we found that lncRNA-NONRATT021203.2 was increased in the CIP rats and that lncRNA-NONRATT021203.2-siRNA could relieve hyperalgesia in these rats. For elucidation of the underlying mechanism, we showed that lncRNA-NONRATT021203.2 could target C-X-C motif chemokine ligand 9 (CXCL9), which was increased in the CIP rats, and that CXCL9-siRNA could relieve hyperalgesia. At the same time, silencing lncRNA-NONRATT021203.2 expression decreased the mRNA and protein levels of CXCL9. Immunofluorescence analysis showed that CXCL9 was mainly expressed in the CGRP-positive and IB4-positive DRG neurons. Further research showed that lncRNA-NONRATT021203.2 and CXCL9 were colocalized in the DRG neurons. Our data suggested that lncRNA-NONRATT021203.2 participated in the CIP in rats and likely mediates the upregulation of CXCL9. The present study provided us with a new potential target for the clinical treatment of cancer-induced pain.

Drought-hardening improves drought tolerance in Nicotiana tabacum at physiological, biochemical, and molecular levels.

BACKGROUND: Drought stress is the most harmful one among other abiotic stresses with negative impacts on crop growth and development. Drought-hardening is a feasible and widely used method in tobacco seedlings cultivation. It has gained extensive interests due to its role in improving drought tolerance. This research aimed to investigate the role of drought-hardening and to unravel the multiple mechanisms underlying tobacco drought tolerance and adaptation. RESULTS: This study was designed in which various drought-hardening treatments (CK (no drought-hardening), T1 (drought-hardening for 24 h), T2 (drought-hardening for 48 h), and T3 (drought-hardening for 72 h)) were applied to two tobacco varieties namely HongHuaDaJinYuan (H) and Yun Yan-100 (Y). The findings presented a complete framework of drought-hardening effect at physiological, biochemical, and gene expression levels of the two tobacco varieties under drought stress. The results showed that T2 and T3 significantly reduced the growth of the two varieties under drought stress. Similarly, among the various drought-hardening treatments, T3 improved both the enzymatic (POD, CAT, APX) and non-enzymatic (AsA) defense systems along with the elevated levels of proline and soluble sugar to mitigate the negative effects of oxidative damage and bringing osmoregulation in tobacco plants. Finally, the various drought-hardening treatments (T1, T2, and T3) showed differential regulation of genes expressed in the two varieties, while, particularly T3 drought-hardening treatment-induced drought tolerance via the expression of various stress-responsive genes by triggering the biosynthesis pathways of proline (P5CS1), polyamines (ADC2), ABA-dependent (SnRK2, AREB1), and independent pathways (DREB2B), and antioxidant defense-related genes (CAT, APX1, GR2) in response to drought stress. CONCLUSIONS: Drought-hardening made significant contributions to drought tolerance and adaptation in two tobacco variety seedlings by reducing its growth and, on the other hand, by activating various defense mechanisms at biochemical and molecular levels. The findings of the study pointed out that drought-hardening is a fruitful strategy for conferring drought tolerance and adaptations in tobacco. It will be served as a useful method in the future to understand the drought tolerance and adaptation mechanisms of other plant species. Drought-hardening improved drought tolerance and adaptation of the two tobacco varieties. T1 indicates drought-hardening for 24 h, T2 indicates drought-hardening for 48 h, T3 indicates drought-hardening for 72 h.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Predictive factors of stone-free rate and complications in patients undergoing minimally invasive percutaneous nephrolithotomy under local infiltration anesthesia.

PURPOSE: To evaluate predictive factors affecting the stone-free rates (SFR) and complications of minimally invasive percutaneous nephrolithotomy (MPCNL) under local infiltration anesthesia (LIA) METHODS: A retrospective analysis was conducted on 976 consecutive patients who underwent MPCNL under LIA from January 2015 to June 2018. Postoperative complications were classified according to modified Clavien classification system. Univariate and multivariate logistic regression analyses were used to determine factors affecting SFR and complications. RESULTS: The pain was acceptable with postoperative visual analog scale (VAS) scores being 3.58, 2.99, 2.25, and 2.07 after 0, 6, 24, and 48 h, respectively. The SFR after primary MPCNL reached 85.7%. Postoperative complications were recorded in 77 patients (7.9%). In the univariate logistic analysis, larger stone size, staghorn stone, and multiple calyxes were significantly associated with lower SFR. The higher American Society of Anesthesiologists (ASA) score, staghorn stone, positive urine culture, multiple tracts, and longer operation time were associated with occurrence of complications. However, hydronephrosis was associated with lower complication rate. Multivariate analysis indicated that larger stone size (P < 0.001) and staghorn stone (P < 0.001) were associated with lower SFR, while development of complications was independently influenced by higher ASA score (P = 0.002), multiple tract (P = 0.004), and staghorn stone (P = 0.028). CONCLUSIONS: MPCNL can be safely and effectively performed under LIA. Stone size and staghorn stone are factors associated with SFR while ASA score, multiple tracts, and staghorn stone are associated with the development of complications. For the first time, we developed a model to predict the SFR and complications in MPCNL under LIA.

Efficacy and safety of transurethral split of prostate for benign prostatic hyperplasia: a meta-analysis.

BACKGROUND: Transurethral resection of the prostate (TURP) is the first choice for the treatment of benign prostatic hyperplasia. However, Transurethral split of prostate (TUSP) also seems to have clear clinical efficacy and clinical promotion value. To better clarify the potential and limitations of this treatment of prostate hyperplasia. This study objectively evaluated the clinical efficacy and safety of TUSP. METHODS: The Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), Wanfang (Wanfang data), and SinoMed databases were searched for relevant studies. We then used Revman Manager 5.3 to perform a meta-analysis of all randomized controlled trials that evaluated the efficacy and safety of TUSP versus the classic surgical procedures commonly used in the clinic. RESULTS: A total of 7 studies involving 592 patients were included. The combined data showed that TUSP can shorten the operation time [MD: -33.68; 95% CI: - 38.45 to - 28.91; P < 0.001], reduce intraoperative blood loss [MD: -56.06; 95% CI: - 62.68 to - 49.43; P < 0.001], shorten the time of indwelling catheter [MD: -1.83; 95% CI: - 1.99 to - 1.67; P < 0.001], shorten the postoperative hospital stay length [MD: -1.61; 95% CI: - 1.90 to - 1.32; P < 0.001] and improved postoperative quality of life score (QOL) [MD: 0.16; 95% CI: 0.02 to 0.29; P = 0.02] compared to traditional surgical approaches. There were no statistically significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax), residual urine volume (RUV), or complications between TUSP and traditional approached. CONCLUSION: TUSP can be an effective alternative for clinical treatment of benign prostatic hyperplasia. Given the limitations of the included studies, more high-quality randomized controlled trials are needed in the future to validate or update the results of this analysis.

Preoperative serum total cholesterol is a predictor of prognosis in patients with renal cell carcinoma: a meta- analysis of observational studies.

PURPOSE: Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic signifi cance of the preoperative serum TC levels for patients with surgically treated RCC. MATERIAL AND METHODS: The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confi dence intervals (CIs) were calculated through inverse variance by using random effects models. RESULTS: Nine cohort studies comprising 15.609 patients were identifi ed. Low preopera- tive serum TC levels were associated with poor cancer-specifi c survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no signifi cant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. CONCLUSIONS: Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.

Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis.

OBJECTIVE: This study aims to design a novel semirigid ureterorenoscope with irrigation and vacuum suction system and a modified ureteral access sheath (UAS) named Sotn ureterorenoscope® (Sotn=ShuoTong Medical Company) to overcome the deficiencies of the current procedure and to improve the efficiency and safety of using Sotn ureterorenoscope® for treatment of upper urinary calculi. MATERIALS AND METHODS: Fifty-eight patients, comprising 31 males and 27 females, were evaluated. The medical records of 58 patients with upper urinary calculi treated with Sotn ureterorenoscope® from March 2015 to June 2017 were retrospectively reviewed at 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 one month after treatment. The secondary outcome was postoperative complication rate. RESULTS: The mean and SD of operative duration was 78.5 (30.4) min, and the mean and SD of stone size was 15.6 (5.6) mm. The primary overall SFR was 89.7% (52/58) and 100% at 1 month follow-up. Complication, which was Clavien I (minor fever managed by antipyretic therapy), was detected in 1.7% (1/58) of the patients. CONCLUSIONS: Sotn ureterorenoscope® is technically feasible, efficacious and safe for treatment of upper urinary calculi because of its advantages of high SFR and low complication rates.

Design and synthesis of fluorogenic substrate-based probes for detecting Cathepsin B activity.

Cathepsin B plays key roles in tumor progression with its overexpression being associated with invasive and metastatic phenotypes and is a primary target of protease activated antibody-directed prodrug therapy. It therefore represents a potential therapeutic and diagnostic target and effort has been made to develop fluorescent probes to report on Cathepsin B activity in cells and animal models of cancer. We have designed, synthesized, and thoroughly evaluated four novel "turn on" probes that employ a lysosomotropic dansylcadaverine dye to report on Cathepsin B activity. Enzyme activity assays using a recombinant human enzyme and cancer cell lysates coupled with confocal microscopy experiments demonstrated that one of the probes, derivatized with the self-immolative prodrug linker p-aminobenzyl alcohol, can selectively report on Cathepsin B in biological samples including live cells.

[Small-cell carcinoma of the prostate: A report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics and improve the clinical treatment of prostatic small-cell carcinoma (PSCC). METHODS: We reported 2 cases of PSCC derived from prostate cancer after treated by androgen blockade and prostate electrotomy and reviewed the relevant literature. RESULTS: Two patients with PSA elevation were diagnosed with prostate cancer by prostatic puncture biopsy and treated by maximum androgen blockade, which reduced their total PSA to the normal level. Later, due to difficult urination, they both underwent prostate electrotomy, followed by chemotherapy or radiotherapy for PSCC confirmed by postoperative pathology. Nevertheless, they died at 8 to 9 months after the discovery of PSCC. CONCLUSIONS: PSCC can derive from prostate cancer after treatment, which may be attributed to the pathological mutation induced by long-term endocrine therapy. PSCC is more malignant than prostate cancer, and its prognosis is poor.

Expression, regulation and function of miR-126 in the mouse choroid vasculature.

MicroRNA miR-126 has been shown to be required for proper angiogenesis in several models. However, its expression, regulation and function in the mouse choroid remain unclear. Our previous data has shown that miR-126 expression is enriched in the endothelial cells (ECs) of the mouse choroid. Here we report that a 5.5 kb Egfl7/miR-126 promoter drives the expression of miR-126 in the choroid ECs during choroidal vascular development. The expression of miR-126 in the ECs is regulated by flow stress likely through Krüppel-like transcriptional factors. miR-126-/- mice show mildly delayed choroidal vascular development, but adult knockout mice develop periphery choroidal vascular lesions. This study suggests that miR-126 is largely dispensable for mouse choroidal development but required for maintaining choroidal vasculature integrity.