Multikingdom characterization of gut microbiota in patients with rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious and common extra-articular disease manifestation. Patients with RA-ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole-metagenome shotgun sequencing on fecal samples from 30 patients with RA-ILD, and 30 with RA-non-ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference-based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA-ILD and RA-non-ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA-ILD), Gemmiger formicilis, and Ruminococcus bromii (RA-non-ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA-ILD and RA-non-ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA-ILD and RA-non-ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research.

Cutaneous leukocytoklastic vasculitis in a patient with ankylosing spondylitis: A case report.

Extra-articular manifestations (EAMs) in ankylosing spondylitis (AS) are common and most extra-articular manifestations such as acute iritis and inflammatory bowel disease are positively correlated with disease activity of AS. Vasculitis is an extra-articular manifestation of AS. However cutaneous leukocytoclastic vasculitis (CLV) is uncommon in AS patients. In this article, we report a case of a 66-year-old female patient who has had AS for long time. Although the patient's articular manifestations were stable, the aortic aneurysm and CLV continued to occur sequentially. This article reminds clinicians that even AS patients with stable articular manifestations should be followed up regularly. All extra-articular manifestations of AS patients should be taken seriously and treated as soon as possible under the guidance of rheumatoid immunologists.

[Retracted] Interaction of YAP1 and mTOR promotes bladder cancer progression.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the immunohistochemical data shown in Fig. 1C on p. 236, and immunofluorescence data featured in Figs. 2G and 5G on p. 237 and 239 respectively, were strikingly similar to data that had appeared in other articles written by different authors at different research institutes which had already been published.  In view of the fact that certain of the data in the above article had already been published at the time of the paper's submission, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 56: 232­242, 2020; DOI: 10.3892/ijo.2019.4922].

Characteristics of primary Sjogren's syndrome with articular manifestations at initial treatment.

Objectives: Articular manifestations have been reported in 19.3%-53.5% of patients with primary Sjogren's syndrome. Our aim was to profile the clinical characteristics of Chinese patients with primary Sjogren's syndrome who presented with articular manifestations at the time of initial treatment. Methods: We conducted a retrospective study of 129 primary Sjogren's syndrome patients admitted to the second Affiliated Hospital of Dalian Medical University between April 2016 and December 2021 for initial treatment. Clinical and serological features, extra-articular involvement, and initial treatment were compared between primary Sjogren's syndrome patients with and without articular manifestations. Results: Fifty-seven (44.2%) primary Sjogren's syndrome patients had articular manifestations (mean age at diagnosis: 53.4 years), of which 42 (73.7%) presented with symmetrical distribution, 21 (36.8%) patients had rheumatoid factor positivity, and 11 (20.0%) patients had anti-cyclic citrullinated peptide antibodies positivity (mean 6.8 RU/mL); imaging examinations showed no signs of structural damage in these patients. The presence of articular manifestations showed positive correlation with anti-cyclic citrullinated peptide antibody level (odds ratio (OR) 1.01, 95% confidence interval (CI): 1.00-1.02; p = 0.049), C-reactive protein level (OR 1.15, 95% CI: 1.10-1.20; p = 0.000), and European League Against Rheumatism Sjogren syndrome disease activity index scores (OR 1.18, 95% CI: 1.11-1.25; p = 0.000). Ninety (69.8%) primary Sjogren's syndrome patients received hydroxychloroquine therapy. Hydroxychloroquine treatment was significantly less frequently used in articular manifestation patients (35 (70.0%) vs 55 (85.9%); p = 0.038). Conclusions: Symmetrical polyarthritis was the most common clinical manifestation of primary Sjogren's syndrome patients with articular manifestations in this cohort. Articular manifestations were associated with higher prevalence of C-reactive protein level, and European League Against Rheumatism Sjogren syndrome disease activity index score.

Diagnosis of neuropsychiatry disorder in patients with anti-MDA5 antibody dermatomyositis: A case report.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) is a rare disease that can be easily misdiagnosed. Anti-MDA5 dermatomyositis is a subtype of DM. It is distinguished by the presence of significant mucocutaneous characteristics, palmar papules, panniculitis, interstitial lung disease (ILD), and clinically amyopathic dermatomyositis (CADM). When combined with rapidly progressing ILD (RP-ILD), anti-MDA5 DM can be fatal. The literature indicates that nervous system involvement is uncommon in patients with anti-MDA5 DM. We report a case of anti-MDA5 DM with neuropsychiatric abnormalities and ILD. The patient suffered from persistent worsening mental disorders, while his ILD was relatively stable. The patient's neuropsychiatric abnormalities gradually subsided after receiving treatment with glucocorticoids, immunoglobulins, and immunosuppressants, leaving only a slow response and memory loss.

Human bone marrow-derived mesenchymal stem overexpressing microRNA-124-3p inhibit DLBCL progression by downregulating the NFATc1/cMYC pathway.

BACKGROUND: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC exosomes carrying microRNA-124-3p in the development of DLBCL. METHODS: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was detected by luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-miR-124-3p on tumor growth were investigated in vivo. RESULTS: MiR-124-3p was expressed at low levels, while NFATc1 was highly expressed in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. The miR-124-3p derived from hBMSCs inhibits tumor growth both in vivo and in vitro via downregulation of the NFATc1/cMYC pathway. CONCLUSION: Human bone marrow-derived mesenchymal stem cell overexpressing microRNA-124-3p represses the development of DLBCL through the downregulation of NFATc1.

Analysis of the effect of holmium laser flexible ureteroscopic intrapelvic drainage in the treatment of parapelvic renal cysts.

Objective: To explore the efficacy, safety, and feasibility of holmium laser flexible ureteroscopic intrapelvic drainage in the treatment of parapelvic renal cysts. Methods: From September 2012 to February 2019, a total of 18 patients, aged from 28 to 62 (mean±standard deviation [SD]: 46.50±9.14) years, were diagnosed with parapelvic renal cysts and treated by holmium laser flexible ureteroscopic intrapelvic drainage. There were 10 males and eight females. All of the parapelvic renal cysts were unilateral, and two cases were complicated with pyelolithiasis. The diameters of the cysts ranged from 4.1 cm to 8.2 cm. Results: All the patients completed the operation successfully in one stage without conversion to open surgery; in two cases, it was difficult to find the cysts during the operation, and the localization was completed by B-ultrasound and percutaneous injection of methylene blue. The mean operative time was 33.89 (SD: 9.68; range: 22-54) min, and the mean hospitalization time was 2.67 (SD: 0.91; range: 2-5) days. Three months and 6 months of follow-up were performed after surgery. The cysts disappeared in 13 (72%) cases, and the diameter of the cysts in five (28%) cases decreased by more than 50%. Conclusion: Holmium laser flexible ureteroscopic intrapelvic drainage in the treatment of parapelvic renal cysts is simple, safe, and effective, and can be used as the first choice for the treatment of parapelvic renal cysts.

Thioredoxin-1 Activation by Pterostilbene Protects Against Doxorubicin-Induced Hepatotoxicity via Inhibiting the NLRP3 Inflammasome.

Background: Doxorubicin (DOX) has been widely used in cancer treatment. However, DOX can cause a range of significant side effects, of which hepatotoxicity is a common one, and therefore limits its clinical use. Pterostilbene (PTS) has been shown to exhibit anti-oxidant and anti-inflammatory effects in the treatment of liver diseases but whether PTS could protect against hepatotoxicity in DOX-treated mice is unknown. Methods: In our study, we use C57/BL6J mice and the HepG2 cell line. We divided the mice in 4 groups: the control, the PTS treatment, the DOX treatment, and the DOX + PTS treatment group. Liver histopathology was judged by performing hematoxylin-eosin and Masson staining. Immunohistochemistry was used to perform the expression of NLRP3. The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and DCFH-DA staining were used to evaluate the oxidative injury. Western blot and real-time PCR were applied to evaluate the expressions of proteins and mRNA. MTT was used to evaluate DOX-induced cell injury and the protective effects of PTS. Recombinant Trx-1 was used to analyze the mechanism of PTS. A TUNEL assay was used to detect apoptosis in DOX-induced HepG2 cells and the protective effects of PTS. Results: PTS ameliorated DOX-induced liver pathological changes and the levels of AST and ALT. PTS also decreased the level of MDA, increased the level of SOD, GSH, and the expression of Trx-1 in DOX-treated mice. PTS decreased the levels of NLRP3 and IL-1ß mRNA and the expressions of their proteins in DOX-treated mice. In addition, PTS also decreased the expression of Cleaved Caspase-3 and BAX and increased the expression of BCL-2. In vitro, after treatment with recombinant Trx-1, ROS and NLRP3 inflammasome were both decreased. Treatment with PTS could rescue the downregulation of Trx-1, decreased the ROS level and the NLRP3 inflammasome, and protected HepG2 cells against DOX-induced apoptosis. Conclusion: The results show that PTS exhibits protective effects against DOX-induced liver injuries via suppression of oxidative stress, fibrosis, NLRP3 inflammasome stimulation, and cell apoptosis which might lead to a new approach of preventing DOX-induced hepatotoxicity.

Ultrathin, elastic, and self-adhesive nanofiber bio-tape: An intraoperative drug-loading module for ureteral stents with localized and controlled drug delivery properties for customized therapy.

During the postoperative management of urinary diseases, oral or intravenous administration of drugs and implanting ureteral stents are usually required, making localized drug delivery by ureteral stent a precise and effective medication strategy. In the traditional drug loading method, the drug was premixed in the implants in production lines and the versatility of drugs was restricted. However, the complex situation in the urinary system fails the possibility of finding a "one fits all" medication plan, and the intraoperative drug-loading of implants is highly desired to support customized therapy. Here, we designed an ultrathin (8 µm), elastic, and self-adhesive nanofiber bio-tape (NFBT) that can easily encapsulate drugs on the stent surface for controllable localized drug delivery. The NFBT exhibited high binding strength to a ureteral stent, a sustained release over 7 d in PBS for hydrophilic drug, and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin (NFT). Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine. The total amount of NFT delivered by the NFBT was about 2.68 wt% of the recommended dose for the systemic administration.

A novel spherical-headed fascial dilator is feasible for second-stage ultrasound guided percutaneous nephrolithotomy: A pilot study.

OBJECTIVE: In second-stage percutaneous nephrolithotomy (PCNL), because the hydronephrosis has been decompressed, the dilated renal pelvis has resolved and the space is small. Consequently, introduction of the tip of the Amplatz dilator can cause injury to the opposite side of the renal-pelvic mucosa. In this study, we report the experimental and initial clinical performance of a spherical-headed fascial dilator developed specifically for second-stage PCNL. METHODS: The novel spherical-headed dilator was compared with existing tapered-headed dilators in configuration and in puncture resistance utilizing a static puncture test. Subsequently, a pilot clinical study was conducted during which patients scheduled to undergo second-stage PCNL from June 2019 to October 2019 in our center were enrolled. A typical ultrasound guided PCNL procedure was performed with the exception that the new spherical-headed fascial dilator was substituted for a tapered-headed one. RESULTS: Experimentally, stab resistance against polyethylene film was significantly increased using the novel spherical-headed dilator compared to the traditional tapered-headed dilators (p<0.005). In the clinical study, the novel dilators were successfully introduced into the renal pelvis and passed down the collecting system in all eight second-stage PCNL cases. There were no cases of renal pelvic perforation or brisk hemorrhage nor need for transfusion. CONCLUSION: The design of the novel spherical-headed fascial dilator avoided the concentration of pressure at the tapered tip of the current Amplatz dilator by increasing the contact area and uniformly distributing and diffusing the pressure. Therefore, it is feasible to use the spherical-headed fascial dilator for second-stage PCNL.

Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling.

Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses.

Biodegradable Anti-Biofilm Fiber-Membrane Ureteral Stent Constructed with a Robust Biomimetic Superhydrophilic Polycationic Hydration Surface Exhibiting Synergetic Antibacterial and Antiprotein Properties.

The biofouling of ureteral stents and subsequent urinary tract infections mainly come from the adsorption and adhesion of proteins and microorganisms and their ensuing proliferation. Although general polycationic surfaces in implants have good antibacterial activities, they suffer from limited durability due to severe protein and bacterial adsorption. Here, a biodegradable and anti-biofilm fiber-membrane structured ureteral stent (FMBUS) with synergetic contact-killing antibacterial activity and antiprotein adsorption is described. The stent is prepared by generating hyperbranched poly(amide-amine)-grafted polydopamine microparticles (≈300 nm) on the surface of fibers by in situ polymerization and Schiff base reactions. The biomimetic surface endows the FMBUS with a positive charge (+21.36 mV) and superhydrophilicity (water contact angle: 0°). As a result, the stents fulfilled the following functions: i) reduced attachment of host protein due to superhydrophilicity (Lysozyme: 92.1%; human serum albumin: 39.4%); ii) high bactericidal activities against contact pathogenic bacteria (contact-killing rate: 99.9999% for both E. coli and S. aureus; antiadhesion rate: 99.2% for E. coli and 99.9999% for S. aureus); iii) biocompatibility in vitro (relative growth rate of L929: >90% on day 3) and in vivo; and iv) gradient biodegradability to avoid a second surgery of stent extraction 1-2 weeks after implantation.

Dream-Experiment: A MR User Interface with Natural Multi-channel Interaction for Virtual Experiments.

This paper studies a set of MR technologies for middle school experimental teaching environments and develops a multi-channel MR user interface called Dream-Experiment. The goal of Dream-Experiment is to improve the traditional MR user interface, so that users can get a real, natural 3D interactive experience like real experiments, but without danger and pollution. In terms of visual presentation, we design multi-camera collaborative registration to realize robust 6-DoF MR interactive space, and also define a complete rendering pipeline to provide improved processing of virtual-real objects' occlusion including translucent devices. In the virtual-real interaction, we provide six interaction modes that support visual interaction, tangible interaction, virtual-real gestures with touching, voice, thermal feeling, and olfactory feeling. After users' testing, we find that Dream-Experiment has better interactive efficiency and user experience than traditional MR environments.

Biomimetic biodegradable Ag@Au nanoparticle-embedded ureteral stent with a constantly renewable contact-killing antimicrobial surface and antibiofilm and extraction-free properties.

Urinary tract infections (UTIs) caused by the contamination of the ureteral stent and the pain associated with secondary stent extractions are worldwide problems in the treatment of urinary tract disorders. Here, we reported a biodegradable, long-term antibacterial, and extraction-free ureteral stent with a constantly renewable contact-killing surface and an antibiofilm function achieved by constructing a hyperbranched poly(amide-amine)-capped Ag shell and Au core nanoparticle (Ag@Au NP)-embedded fiber membrane-structured poly(glycolic acid)/poly(lactic-co-glycolic acid) (PGA/PGLA) ureteral stent. The ureteral stent showed fast contact-killing properties, i.e., 5 min for Escherichia coli and 10 min for Staphylococcus aureus, with an inhibition rate higher than 99%. In addition, gradient degradation of PGA/PGLA endowed the stent with a self-cleaning property and long-term antibacterial function by continuous exfoliation of the stent surface, thereby exposing the inner Ag@Au NPs and eliminating adherent bacteria and proteins. Subsequently, in the 16-day in vitro degradation test, the stent showed durable bactericidal activity, less total release of Ag and Au elements (6.7%, ~8 µg), and low cytotoxicity (with a relative growth rate of >80% of L929 cells). In vivo experiments on a farm pig model showed that the stent exhibited a remarkable antibiofilm property and reduced the level of inflammatory and necrotic cells. After seven days of implantation, the stent showed a gradient degradation behavior and maintained structural integrity without the presence of any large fragments in the urinary system according to the B-ultrasonic examination. The as-developed biodegradable and renewable contact-killing antibacterial strategy was efficient in preparing the ureteral stent with antibiofilm and extraction-free properties to treat stent-induced UTI. Statement of significance This study presents a customized antibiofilm solution for biodegradable implants. Two particularly important aspects of this work are as follows.

It is efficient to monitor the status of implanted ureteral stent using a mobile social networking service application.

Forgotten ureteral stents (FUS) is a great threat to both patients and doctors. Applications on smartphones can significantly reduce the incidence of FUS. But existing applications do not have instant notification and consultation functions. To implement those function, we developed a ureteral stent tracking system embedded in a social networking service application, WeChat. "Ureteral Stent Tracking System" was developed on WeChat, a social media application using by 1.4 million active users. The study consecutively enrolled patients who underwent ureteral stent installation from April 2018 to July 2018. Each patient's information was recorded on the smartphone by the urologists to create a document immediately after the surgery. The system sends notifications twice a week to both patients and clinicians via the message function of WeChat. A total of 183 patients were enrolled. The most senior patient enrolled was 73 years old. 156 (85.2%) patients underwent stent extraction before the scheduled time. 22 did not undergo stent extraction before the scheduled time because of urinary tract infection or stone residue. They underwent stent extraction within 1 month after the scheduled time. Two patients did not come to the hospital until we had made a phone call to them, though they had received notification from the online system. During the study, no patient was lost-to-follow up. In bilateral stents cases, no stent was forgotten after extraction surgery. A total of 85 (46.4%) patients consulted 132 issues in the system. 52 (39.4%) patients complained about hematuria. 36 (27.3%) patients reported lower urinary tract symptoms. All the consultations were answered within 24 h. "Ureteral Stent Tracking System" implement instant notification and consultation functions via WeChat. It helps urologists to manage indwelling ureteral stents and to reduce the incidence of FUS efficiently.

Interaction of YAP1 and mTOR promotes bladder cancer progression.

Yes­associated protein 1 (YAP1) and mammalian target of rapamycin (mTOR) signaling pathways have been found to be deregulated in bladder cancer and accelerate the malignant progression of bladder cancer. However, the crosstalk between YAP1 and mTOR and its role in bladder cancer progression remains unclear. The aim of the present study was to investigate this crosstalk and the results revealed that the expression of YAP1 and mTOR was elevated in bladder cancer tissues compared with that in adjacent normal tissues. Knockdown of either mTOR or YAP1 with siRNA transfection significantly repressed the proliferation ability and induced apoptosis of HT­1376 and J82 bladder cancer cells, particularly when YAP1 and mTOR were downregulated simultaneously. Upregulation of mTOR increased the mRNA and protein levels of YAP1 and enhanced its nuclear accumulation. In turn, YAP1 upregulation increased mTOR expression, reduced its protein degradation and increased its stability. In addition, immunofluorescence and Duolink assays demonstrated that YAP1 and mTOR were co­localized in the nucleus. Immunoprecipitation assay demonstrated that the YAP1 protein was able to bind to the mTOR protein. Moreover, YAP1 combined with S­phase kinase­associated protein 2 (SKP2) and positively regulated its expression. Furthermore, the promotion of cell growth and inhibition of cell apoptosis induced by YAP1 overexpression were abolished when SKP2 was downregulated in HT­1376 and J82 cells. Taken together, the findings of the present study indicated that the crosstalk between YAP1 and mTOR plays a pivotal role in accelerating the progression of bladder cancer, which may provide new insights into the role of the YAP1/mTOR axis in the occurrence and development of bladder cancer.

Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer.

Kaempferol is a well-known natural flavonol reported to be a potential treatment for multiple cancers. In this study, we demonstrated that cell growth of androgen-sensitive LNCaP cells could be inhibited 33% by 5 µM kaempferol, around 60% by 10 µM kaempferol, and almost 100% by 15 µM kaempferol. Also, kaempferol showed relatively limited effect on PC-3 cells and nonmalignant RWPE-1 cells. In the presence of DHT, the IC50 for kaempferol was 28.8 ± 1.5 µM in LNCaP cells, 58.3 ± 3.5 µM in PC-3 cells, and 69.1 ± 1.2 µM in RWPE-1 cells, respectively. Kaempferol promotes apoptosis of LNCaP cells in a dose-dependent manner in the presence of dihydrotestosterone (DHT). Then, luciferase assay data showed that kaempferol could inhibit the activation of androgen receptors induced by DHT significantly. The downstream targets of androgen receptors, such as PSA, TMPRSS2, and TMEPA1, were found decreased in the presence of kaempferol in qPCR data. It was then confirmed that the protein level of PSA was decreased. Kaempferol inhibits AR protein expression and nuclear accumulation. Kaempferol suppressed vasculogenic mimicry of PC-3 cells in an in vitro study. In conclusion, kaempferol is a promising therapeutic candidate for treatment of prostate cancer, where the androgen signaling pathway as well as vasculogenic mimicry are involved.

Blockage of macrophage migration inhibitory factor (MIF) suppressed uric acid-induced vascular inflammation, smooth muscle cell de-differentiation, and remodeling.

Hyperuricemia contributes to vascular injury and dysfunction, yet the potential mechanisms are not well understood. Uric acid (UA) has been found to stimulate macrophage migration inhibitory factor (MIF) up-regulation in renal tubules from rats subjected to UA-induced nephropathy. Given that MIF is able to induce vascular smooth muscle cell (VSMC) de-differentiation (from contractile state to a secretory state), we thus hypothesized that UA-induced vascular injury is via up-regulating of MIF in VSMCs, which enhancing vascular inflammation and VSMC transition. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured circulating and vascular MIF levels under UA stimulation at 6 h, day 1, and 14. We tested the efficacy of MIF inhibitor (10 mg/kg, twice/day, 14 days) on UA-induced vascular inflammation and remodeling. High plasma level of UA induced vascular MIF release into the plasma at acute phase. In the chronic phase, the protein level of MIF is up-regulated in the vessels. MIF inhibitor suppressed vascular inflammatory responses, repressed VSMC de-differentiation, and attenuated vascular remodeling and dysfunction following UA stimulation. Knockdown of MIF in cultured VSMCs repressed UA-induced de-differentiation. Our results provided a novel mechanism for MIF-mediated vascular injury in response to UA stimulation, and suggested that anti-MIF interventions may be of therapeutic value in hyperuricemic patients.

Unilateral Renal Tumor Cryoablation and Contralateral Radical Nephrectomy of Bilateral Renal Tumors by Transumbilical 3D Multichannel Laparoendoscopic Single-Site Surgery.

Background: Unilateral renal tumor cryoablation and contralateral radical nephrectomy of bilateral renal tumors were performed by transumbilical three-dimensional (3D) multichannel laparoendoscopic single-site (LESS) surgery, in an attempt to verify the feasibility and safety of the procedure, sum up the operational experience, and evaluate the surgical outcome. Case Presentation: This was a 47-year-old female patient with a body mass index of 27.34 kg/m2 without backache, low back pain, hematuria, urinary urgency, frequent urination, dysuria, and other symptoms. Contrast-enhanced CT scan of the kidney on admission showed four masses in the left kidney and two masses in the right kidney. Preoperative serum creatinine (SCr) was 87 µmol/L. Operation was performed under general anesthesia by first laying the patient in a left lateral position. A 2-cm longitudinal transumbilical skin incision was made to expose the right kidney for complete dissection of the two tumors. First, puncture biopsy was performed, and then two freeze-thaw cryoablation cycles for the two tumors were performed. At last, the patient was laid in a right lateral position for radical nephrectomy of the left kidney. The operative duration, cryoablation time, and estimated blood loss were 200 minutes, 40 minutes, and 100 mL, respectively. Postoperative pathological examination revealed clear-cell renal cell carcinoma. The right glomerular filtration rate tested was 42.36 mL/minute and SCr was 131 µmol/L at day 5 after surgery. There was no evidence of contrast enhancement at the cryoablative region as shown by renal contrasted CT scan performed 4 days after surgery and renal contrasted MRI scan performed 6 weeks after surgery, indicating that there was no tumor remnant or recurrence. Conclusion: Our preliminary experience shows that the treatment of bilateral renal tumors with unilateral renal tumor cryoablation and contralateral radical nephrectomy by transumbilical 3D LESS is safe, feasible, and effective. It may prove to be a viable option for patients with significant comorbidities and an insensitive treatment intention.

Phosphorous fractions in soils of rubber-based agroforestry systems: Influence of season, management and stand age.

Rubber-based agroforestry system is a vital management practice and its productivity is often controlled by soil phosphorus (P) nutrient, but little information is available on P fractions dynamics in such system. The aim of this study was to examine the seasonal, management and stand age effects on P fractions, acid phosphatase activity, microbial biomass P, other physical-chemical properties and litter and roots in four systems: 10-year-old rubber mono- (YM) and intercropping (YI) with N-fixing species (NFS), 22-year-old mono- (MM) and intercropping (MI) in Xishuangbanna, Southwestern China. Most P fractions varied seasonally at different depths, with highest values in the fog-cool season (i.e. labile P at 5-60cm, non-labile P and total P at 30-60cm). By contrast, moderately labile P varied little over time, except in MI that had lower values in the rainy season. Compared with their monoculture counterparts, YI doubled resin-Pi concentration but decreased NaHCO3-extractable P, HCl-Pi and residual-Po at the 0-30cm depth, whereas MI had hardly any changes in P species at the 60-cm depth. Surprisingly, residual-Po was enriched down to the deepest soil (30-60cm) in both YI and MI in the fog-cool season. All P fractions, except NaOH0.1-Pi, were greatly reduced with increasing stand age. In addition to plants uptake, these changes can be explained by seasonality in soil environments (e.g. moisture, temperature, pH and microbial activity) and decomposition of litter and roots. Moreover, YI decreased labile Po stock, but MI increased moderately labile Pi at the 60-cm depth across seasons. The results imply that a large amount of residual-Po exists in acidic Oxisol from China and that they can be reasonably exploited to reduce the application of P fertilizers, highlighting the importance of Po pool. Taken together, intercropping mature rubber plantation with NFS appears to be an effective way to enhance productivity while maintaining adequate soil P concentration over the long run.