Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study.

BACKGROUND: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM. METHODS: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan-Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2. RESULTS: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram. CONCLUSIONS: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM.

Integrating image and gene-data with a semi-supervised attention model for prediction of KRAS gene mutation status in non-small cell lung cancer.

KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S2MMAM). S2MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2MF-CN). S2MMAM facilitates the execution of the classification task by transferring the useful information captured in SMF-SN to the S2MF-CN to improve the model prediction accuracy. In SMF-SN, we propose a Triple Attention-guided Feature Aggregation module for obtaining segmentation features that incorporate high-level semantic abstract features and low-level semantic detail features. Segmentation features provide pre-guidance and key information expansion for S2MF-CN. S2MF-CN shares the encoder and decoder parameters of SMF-SN, which enables S2MF-CN to obtain rich classification features. S2MF-CN uses the proposed Intra and Inter Mutual Guidance Attention Fusion (I2MGAF) module to first guide segmentation and classification feature fusion to extract hidden multi-scale contextual information. I2MGAF then guides the multidimensional fusion of genetic data and CT image data to compensate for the lack of information in single modality data. S2MMAM achieved 83.27% AUC and 81.67% accuracy in predicting KRAS gene mutation status in NSCLC. This method uses medical image CT and genetic data to effectively improve the accuracy of predicting KRAS gene mutation status in NSCLC.

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

BACKGROUND: Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. OBJECTIVE: This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. METHODS: Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. RESULTS: A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. CONCLUSIONS: TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.

Integration of basement membrane-related genes in a risk signature for prognosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by high heterogeneity and recurrence rates, posing significant challenges for stratification and treatment. Basement membrane-related genes (BMGs) play a crucial role in tumor initiation and progression. Clinical and transcriptomic data of ccRCC patients were extracted from TCGA and GEO databases. We employed univariate regression and LASSO-Cox stepwise regression analysis to construct a BMscore model based on BMGs expression level. A nomogram combining clinical features and BMscore was constructed to predict individual survival probabilities. Further enrichment analysis and immune-related analysis were conducted to explore the enriched pathways and immune features associated with BMGs. High-risk individuals predicted by BMscore exhibited poorer overall survival, which was consistent with the validation dataset. BMscore was identified as an independent risk factor for ccRCC. Functional analysis revealed that BMGs were related to cell-matrix and tumor-associated signaling pathways. Immune profiling suggests that BMGs play a key role in immune interactions and the tumor microenvironment. BMGs serve as a novel prognostic predictor for ccRCC and play a role in the immune microenvironment and treatment response. Targeting the BM may represent an alternative therapeutic approach for ccRCC.

R-ketorolac ameliorates cancer-associated cachexia and prolongs survival of tumour-bearing mice.

BACKGROUND: Cancer-associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation. Several non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested for CAC treatment, yet no single medication has proven reliable. R-ketorolac (RK) is the R-enantiomer of a commonly used NSAID. The effect of RK on CAC has not yet been evaluated. METHODS: Ten- to 11-week-old mice were inoculated with C26 or CHX207 cancer cells or vehicle control (phosphate-buffered saline [PBS]). After cachexia onset, 2 mg/kg RK or PBS was administered daily by oral gavage. Body weight, food intake and tumour size were continuously measured. At study endpoints, blood was drawn, mice were sacrificed and tissues were excised. Immune cell abundance was analysed using a Cytek® Aurora spectral flow cytometer. Cyclooxygenase (COX) activity was determined in lung homogenates using a fluorometric kit. Muscle tissues were analysed for mRNA and protein expression by quantitative real-time PCR and western blotting analysis, respectively. Muscle fibre size was determined on histological slides after haematoxylin/eosin staining. RESULTS: Ten-day survival rate of C26-bearing animals was 10% while RK treatment resulted in a 100% survival rate (P = 0.0009). Chemotherapy resulted in a 10% survival rate 14 days after treatment initiation, but all mice survived upon co-medication with RK and cyclophosphamide (P = 0.0001). Increased survival was associated with a protection from body weight loss in C26 (-0.61 ± 1.82 vs. -4.48 ± 2.0 g, P = 0.0004) and CHX207 (-0.49 ± 0.33 vs. -2.49 ± 0.93 g, P = 0.0003) tumour-bearing mice treated with RK, compared with untreated mice. RK ameliorated musculus quadriceps (-1.7 ± 7.1% vs. -27.8 ± 8.3%, P = 0.0007) and gonadal white adipose tissue (-18.8 ± 49% vs. -69 ± 15.6%, P = 0.094) loss in tumour-bearing mice, compared with untreated mice. Mechanistically, RK reduced circulating interleukin-6 (IL-6) concentrations from 334 ± 151 to 164 ± 123 pg/mL (P = 0.047) in C26 and from 93 ± 39 to 35 ± 6 pg/mL (P = 0.0053) in CHX207 tumour-bearing mice. Moreover, RK protected mice from cancer-induced T-lymphopenia (+1.8 ± 42% vs. -49.2 ± 12.1% in treated vs. untreated mice, respectively). RK was ineffective in ameliorating CAC in thymus-deficient nude mice, indicating that the beneficial effect of RK depends on T-cells. CONCLUSIONS: RK improved T-lymphopenia and decreased systemic IL-6 concentrations, resulting in alleviation of cachexia and increased survival of cachexigenic tumour-bearing mice, even under chemotherapy and independent of COX inhibition. Considering its potential, we propose that the use of RK should be investigated in patients suffering from CAC.

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

Ultra-fast, sensitive and low-cost real-time PCR system for nucleic acid detection.

Nucleic acid detection directly identifies the presence of pathogenic microorganisms and has various advantages, such as high sensitivity, commendable specificity and a short window period, and has been widely used in many fields, such as early tumor screening, prenatal diagnosis and infectious disease detection. Real-time PCR (polymerase chain reaction) is the most commonly used method for nucleic acid detection in clinical practice, but it always takes about 1-3 hours, severely limiting its application in particular scenarios such as emergency testing, large-scale testing and on-site testing. To solve the time-consuming problem, a real-time PCR system based on multiple temperature zones was proposed, which realized the speed of temperature change of biological reagents from 2-4 °C s-1 to 13.33 °C s-1. The system integrates the advantages of fixed microchamber-type and microchannel-type amplification systems, including a microfluidic chip capable of fast heat transfer and a real-time PCR device with a temperature control strategy based on the temperature difference. The detection of HCMV biological samples using the real-time PCR system in this research took only 15 min, which was 75% shorter compared to the commercial qPCR instrument such as BIO-RAD, and the detection sensitivity remained essentially the same. The system could complete nucleic acid detection within 9 min under extreme conditions, characterized by fast detection speed and high sensitivity, providing a promising solution for ultra-fast nucleic acid detection.

The human microbiome links to prostate cancer risk and treatment (Review).

Prostate cancer (Pca) is the second most common cancer type worldwide. Microorganisms colonized in different body parts may affect the development/progression and treatment of Pca through direct or indirect interactions. The composition of microorganisms in different colonization sites and their effects on Pca may differ. In recent years, several studies have focused on the differences in the microbiota of patients with Pca, and dysbiosis may affect the inflammatory status, hormone levels and microbial metabolites leading to Pca progression. However, little is known about the interaction between Pca treatment and microorganisms; for example, how androgen deprivation therapy and androgen receptor axis­targeting therapeutics for Pca affect microbiota composition and metabolism, and how the microbiota affects treatment response in patients with Pca remain to be understood. The present review explored the current studies on the relevance of microbiota to Pca progression and treatment to provide direction for future microbiome­Pca research. Due to the complexity of the potential interconnections between Pca and the microbiota, further investigation is critical.

Ultrafast Microfluidic PCR Thermocycler for Nucleic Acid Amplification.

The polymerase chain reaction (PCR) is essential in nucleic acid amplification tests and is widely used in many applications such as infectious disease detection, tumor screening, and food safety testing; however, most PCR devices have inefficient heating and cooling ramp rates for the solution, which significantly limit their application in special scenarios such as hospital emergencies, airports, and customs. Here, we propose a temperature control strategy to significantly increase the ramp rates for the solution temperature by switching microfluidic chips between multiple temperature zones and excessively increasing the temperature difference between temperature zones and the solution; accordingly, we have designed an ultrafast thermocycler. The results showed that the ramp rates of the solution temperature are a linear function of temperature differences within a range, and a larger temperature difference would result in faster ramp rates. The maximum heating and cooling ramp rates of the 25 µL solution reached 24.12 °C/s and 25.28 °C/s, respectively, and the average ramp rate was 13.33 °C/s, 6-8 times higher than that of conventional commercial PCR devices. The thermocycler achieved 9 min (1 min pre-denaturation + 45 PCR cycles) ultrafast nucleic acid amplification, shortening the time by 92% compared to the conventional 120 min nucleic acid amplification, and has the potential to be used for rapid nucleic acid detection.

Effect of X-ray radiation on the pharmacokinetics of apatinib in vivo in rats.

Purpose: The "radiotherapy-pharmacokinetic" ("RT-PK") phenomenon refers to the fact that radiation can significantly alter the pharmacokinetic behavior of a drug. At present, it is not clear whether there is an "RT-PK" phenomenon that can affect apatinib during concurrent chemoradiotherapy. In this study, we used a rat irradiation model to study the effects of X-ray radiation on absorption, tissue distribution, and excretion of apatinib. Method: Healthy Sprague-Dawley (SD) rats were randomly divided into control and radiation groups. The radiation group was given an appropriate dose of abdominal X-ray radiation, while the control group was not given irradiation. After 24 h of recovery, both groups were given apatinib solution 45 mg/kg by gavage. A quantitative LC-MS/MS method was developed to determine the concentration of apatinib in the rats, so as to compare the differences between the control and radiation groups and thus investigate the modulating effect of radiation on the pharmacokinetics of apatinib in rats. Results: After abdominal X-ray irradiation, the area under the curve (AUC0-t) of apatinib in rat plasma decreased by 33.8% and 76.3% at 0.5 and 2 Gy, respectively. Clearance (CL) and volume of distribution (Vd) increased and were positively correlated with radiation dose. X-ray radiation significantly reduced the concentration of apatinib in the liver and small intestine, and there was no tissue accumulation. In excretion studies, we found that X-ray radiation reduced the cumulative excretion of apatinib in feces and urine by 11.24% and 86.17%, respectively. Conclusion: Abdominal X-ray radiation decreased plasma exposure, tissue distribution, and excretion of apatinib in rats, suggesting that the RT-PK phenomenon affects apatinib. We speculate that this RT-PK phenomenon is closely related to changes in metabolic enzymes in vivo. In clinical practice, when apatinib is combined with radiotherapy, attention should be paid to adjusting the dose of apatinib and optimizing the treatment plan to alleviate the adverse effects of this RT-PK phenomenon.

Analysis of Key Genes for Slow Transit Constipation Based on RNA Sequencing.

Purpose: This study aims to identify key genes in slow transit constipation (STC). We also sought to explore the potential link between STC and colorectal cancer. Patients and Methods: mRNA expression profiles were obtained by RNA sequencing, and differentially expressed genes were identified. Functional enrichment analysis and a protein-protein interaction (PPI) network was explored, and differentially expressed genes common to STC and colorectal cancer were examined. Analysis of the effect of constipation and colorectal cancer common genes on the overall survival of colorectal cancer patients based on GEPIA database. Results: Functional enrichment showed that significantly different genes are related to lymphocyte chemotaxis, positive regulation of inflammatory response, cellular response to tumor necrosis factor, extracellular region, extracellular space and chemokine activity. The hub gene for STC was found in the PPI network. In addition, AQP8 and CFD were common differential genes for STC and colorectal cancer. AQP8 affects overall survival in patients with colorectal cancer. Conclusion: Our findings will contribute to understanding the pathology of STC at the molecular level, with the first discovery that AQP8 may be a hub gene in the transition from STC to colorectal cancer.

The Efficacy and Safety of HoLEP for Benign Prostatic Hyperplasia With Large Volume: A Systematic Review and Meta-Analysis.

This meta-analysis was to evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with large volume. PubMed, Embase, and Cochrane Library databases (until March 2022) were used to search related randomized controlled trials. A total of 11 studies including 1,258 patients were involved. HoLEP could significantly decrease the length of hospital stay and accelerate recovery. In subanalysis, HoLEP had better perioperative outcomes than bipolar transurethral resection of the prostate (B-TURP) and bipolar transurethral enucleation of the prostate (BPEP). The improvement in operative time and enucleation time was better in thulium laser enucleation of the prostate (ThuLEP) than HoLEP. In the follow-up period, the HoLEP decreased post-void residual urine (PVR) in short-term intervals and improved patients' maximum flow rate (Qmax) and prostate-specific antigen (PSA) in mid- and long-term intervals. In subanalysis, HoLEP presented significant improvements in Qmax, PSA, and quality of life (QoL) than B-TURP, and HoLEP could also improve Qmax than ThuLEP after 6 months of surgery. The HoLEP reduced the risk of postoperative bleeding compared with other surgeries in safety. In our study, we confirmed the advantages of HoLEP in treating BPH when the prostate size was larger than 80 mL, which indicated that HoLEP could be the best choice for treatment of large volume of prostate.

Efficacy and Adverse Events of PD-1 Inhibitors in Patients With Advanced Urothelial Carcinoma From a Real-World Experience.

Background: Programmed death 1 (PD-1) inhibitors-tislelizumab, toripalimab, camrelizumab, and sintilimab-are used for advanced urothelial carcinoma (UC) in China. To date, the efficacy and adverse events (AEs) of these PD-1 inhibitors have been poorly reported for advanced UC. Methods: We reviewed 118 patients treated with PD-1 inhibitors for advanced UC from July 2019 to October 2021 at Yantai Yuhuangding Hospital. Patient data were obtained from hospital records and telephone follow-ups. The safety and efficacy of PD-1 inhibitors were assessed by RESIST and Common Terminology Criteria for Adverse Events (version 4.0), respectively. Results: During a median follow-up period of 6 months, 112 patients (95%) experienced AEs; of these, 104 (88%) were grade 1-2 AEs, and 60 (51%) were grade 3-4 AEs. The most common AE was anemia, and no patients died as a result of treatment. A subanalysis according to treatment method (PD-1 inhibitor vs. PD-1 inhibitor plus chemotherapy) was performed. The incidence of grade 1-2 AEs was not different between the groups (85% vs. 94%), but combination therapy significantly increased grade 3-4 AEs (32% vs. 89%). Monotherapy and combination therapy also did not differ with regard to immune-related AEs of grades 1-2 (13% vs. 22%) or grades 3-4 (1% vs. 6%). In efficacy, complete response was not observed, but 33 patients (28%) had partial response, 30 (25%) had stable disease, and 47 had progressive disease (40%). The overall response and disease control rates were 28% and 53%, respectively. The preliminary efficacy of disease control was better with combination therapy versus monotherapy (78 vs. 43%). Conclusion: PD-1 inhibitors show promising tolerance and efficacy in advanced UC. PD-1 inhibitors combined with chemotherapy offered better disease control but had more grade 3-4 AEs. The clinical use of combination therapy warrants caution.

Transarterial chemoembolization (TACE) plus apatinib-combined therapy versus TACE alone in the treatment of intermediate to advanced hepatocellular carcinoma patients: A real-world study.

BACKGROUND: Apatinib exhibits the synergistic effect with transarterial chemoembolization (TACE) though inhibiting the neoangiogenetic reaction caused by TACE. In this real-world study, we aimed to evaluate the efficacy and safety of TACE plus apatinib-combined therapy (ACT) in intermediate to advanced hepatocellular carcinoma (HCC) patients. METHODS: Data from 168 intermediate to advanced HCC patients who received TACE alone (N = 49) or TACE plus ACT (N = 119) were extracted. Besides, ACT was defined as apatinib with or without other therapy, such as arsenic trioxide, microwave ablation and radioactive seed implantation. RESULTS: In TACE plus ACT group, the median overall survival (OS) was 30 months (95% confidence interval (CI): 24-40 months) with 1-year, 3-year and 5-year OS rate of 84.0%, 41.2% and 21.5%, respectively. While in TACE group, the median OS was only 14 months (95%CI: 11-17 months) with 1-year, 3-year and 5-year OS rate of 55.1%, 18.4% and 16.1%, separately. By comparation, the OS was prolonged in TACE plus ACT group compared with TACE group (P<0.001). After adjusted by multivariate Cox's regression analysis, TACE plus ACT (vs. TACE) independently related to the longer OS (hazard ratio: 0.504, P = 0.001). In TACE plus ACT group, the most frequent adverse events included hand-foot syndrome (95.8%), hypertension (95.8%), fatigue (90.8%), albuminuria (85.7%), anorexia (79.0%), diarrhea (66.4%), myelosuppression (58.8%), nausea/vomiting (49.6%) and abdominal pain (39.5%), besides, no grade 4 adverse events and treatment-related death occurred. CONCLUSION: TACE plus ACT is a promising treatment choice for the intermediate to advanced HCC patients.

Adverse Effects and Toxicity of Immune Checkpoint Inhibitors For Patients With Urothelial Carcinoma.

Urothelial carcinoma (UC) occupies a high incidence among all the genitourinary malignancies. Immune checkpoint inhibitors (ICIs), as alternative treatments of metastatic urothelial carcinoma (mUC), have been applied in the treatment of mUC after chemotherapy failure, with comparable efficacy and safety. ICIs can enhance anti-tumor T cell reactivity and promote immune control over the cancerous cells by blocking cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the combination of PD-1 and PD-L1. In the treatment of urothelial carcinoma, ICIs show obvious advantage and can enhance survival rates. However, their adverse effects are gradually manifested with increasing clinical applications. Therefore, we review the adverse effects and toxicity of ICIs in patients with UC, aiming to provide sound theoretical references and therapeutic strategies for their clinical application.

Centromere-Specific Retrotransposons and Very-Long-Chain Fatty Acid Biosynthesis in the Genome of Yellowhorn (Xanthoceras sorbifolium, Sapindaceae), an Oil-Producing Tree With Significant Drought Resistance.

In-depth genome characterization is still lacking for most of biofuel crops, especially for centromeres, which play a fundamental role during nuclear division and in the maintenance of genome stability. This study applied long-read sequencing technologies to assemble a highly contiguous genome for yellowhorn (Xanthoceras sorbifolium), an oil-producing tree, and conducted extensive comparative analyses to understand centromere structure and evolution, and fatty acid biosynthesis. We produced a reference-level genome of yellowhorn, ∼470 Mb in length with ∼95% of contigs anchored onto 15 chromosomes. Genome annotation identified 22,049 protein-coding genes and 65.7% of the genome sequence as repetitive elements. Long terminal repeat retrotransposons (LTR-RTs) account for ∼30% of the yellowhorn genome, which is maintained by a moderate birth rate and a low removal rate. We identified the centromeric regions on each chromosome and found enrichment of centromere-specific retrotransposons of LINE1 and Gypsy in these regions, which have evolved recently (∼0.7 MYA). We compared the genomes of three cultivars and found frequent inversions. We analyzed the transcriptomes from different tissues and identified the candidate genes involved in very-long-chain fatty acid biosynthesis and their expression profiles. Collinear block analysis showed that yellowhorn shared the gamma (γ) hexaploidy event with Vitis vinifera but did not undergo any further whole-genome duplication. This study provides excellent genomic resources for understanding centromere structure and evolution and for functional studies in this important oil-producing plant.

Efficacy of magnetic stimulation for female stress urinary incontinence: a meta-analysis.

AIM: This meta-analysis aimed to evaluate the efficacy of magnetic stimulation (MS) in treating female stress urinary incontinence (SUI) and providing an alternative treatment for patients who are unwilling to undergo surgery. METHODS: Randomized controlled trials (RCTs) that evaluated MS as a remedy for female SUI were retrieved from various electronic databases, including MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry system. Moreover, reference lists for related papers were carefully screened for relevant studies. RESULTS: A total of six RCTs evaluating the effect of MS in treating female SUI were included in this study. Compared with the placebo group, the MS group exhibited higher quality-of-life scores [mean difference (MD) 0.59, 95% credibility interval (CI) 0.23-0.95; p = 0.001] and lower International Consultation on Incontinence Questionnaire scores (MD -3.93, 95% CI -5.85 to -2.01; p < 0.0001). Moreover, they exhibited a higher objective cure rate (odds ratio 8.49, 95% CI 3.08-23.37). In addition, MS treatment reduced the number of episodes of urinary incontinence (MD -1.42, 95% CI -2.24 to -0.59; p = 0.0007) and urine loss on pad test (MD -4.67, 95% CI -8.05 to -1.28; p = 0.007). There were no significant treatment-related adverse reactions. CONCLUSION: This study evaluated the efficacy and safety of MS in the treatment of female SUI. The results have important implications for patients who do not wish to undergo surgical therapy. We found that MS treatment for SUI has positive outcomes, however, future studies should aim at establishing the best protocol for optimizing the therapeutic effect.

Impact of differential ureteral stent diameters on clinical outcomes after ureteroscopy intracorporeal lithotripsy: A systematic review and meta-analysis.

In this meta-analysis we assessed whether the diameter of ureteral stents (4.7-5-Fr, 6-Fr) has an impact on the rate of occurrence of urinary tract symptoms and complications after successful URS and intracorporeal lithotripsy. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A rigorous search for relevant studies published in MEDLINE, Embase, and the Cochrane Controlled Trials Register was conducted to find informative randomized controlled trials. The reference lists of relevant articles were also manually searched and reviewed. The protocol was prospectively registered at PROSPERO (CRD42020202164). All statistical evaluations were performed using RevMan software version 5.3.0. Seven articles comprising 547 patients were included in the meta-analysis. After placement of ureteral stents with different diameters for approximately 1 week, we found that ureteral stents with smaller diameters (4.7-5-Fr) were associated with significant improvements in the main domain scores on the Ureteral Stent Symptom Questionnaire, such as urinary symptoms (mean difference -4.47, 95% confidence interval -5.87 to -3.08; P < 0.00001) and body pain (mean difference -2.48, 95% confidence interval -4.37 to -0.59; P = 0.01), but poor outcomes in stent migration compared to ureteral stents with a 6-Fr diameter (odds ratio 3.00, 95% confidence interval 1.06-8.51; P = 0.04). However, there were no significant differences in Ureteral Stent Symptom Questionnaire scores with regard to work performance (mean difference -0.56, 95% confidence interval -2.52 to 1.40; P = 0.58), general health (mean difference -2.29, 95% confidence interval -4.95 to 0.37; P = 0.09), additional problems (mean difference -0.43, 95% confidence interval -1.02 to 0.15; P = 0.15), and complications such as fever (odds ratio 0.75, 95% confidence interval 0.24-2.39; P = 0.63). Ureteral stents with a diameter of 4.7-5-Fr have better outcomes than those with a diameter of 6-Fr, based on the Ureteral Stent Symptom Questionnaire pain and urinary tract symptoms scores. However, they are more prone to migration compared to those with a larger diameter.

C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages.

BACKGROUND: Colon cancer is one of the most common cancers with a high incidence and high mortality. Chemokines play a crucial role in the development of cancer. METHODS: Here, qRT-PCR was performed to detect gene expression. Western blot and immunohistochemistry were implemented to examine the expression of C-C motif chemokine ligand 14 (CCL14) in colon tumors. Besides, the expression of CD68 and CD206 in tumors was measured by immunohistochemistry. The percentages of M1- and M2-polarized macrophages were detected by flow cytometry. Furthermore, CCK-8 assay was performed to detect cell proliferation, and Transwell assay for cell invasion. RESULTS: CCL14 was decreased in both colon tumors and colon cancer cells, and many tumor-associated macrophages (TAMs) infiltrated into the tumor. An increase CCL14 inhibited colon cancer cell proliferation. Importantly, CCL14 promoted THP-1 to M1 polarization induced by LPS and IFN-γ, and inhibited THP-1 to M2 polarization induced by IL-4 and IL-13. Besides, CCL14 enhanced the inhibition of M1-polarized macrophages to colon cancer cell proliferation and invasion, and reversed the promotion of M2-polarized macrophages to cell proliferation and invasion. CONCLUSION: Our data demonstrated that CCL14 inhibited the proliferation and invasion of colon cancer cells through suppressing the formation of M2-like TAMs.