Decomposition of micromotion at the head-neck interface in total hip arthroplasty during walking.

Fretting corrosion as one of the leading causes for failure of modular hip prostheses has been associated with micromotion at head-neck taper junction. Decomposition of micromotion is helpful to promote the development of more realistic experiments investigating failure mechanisms of the head-neck junction in total hip arthroplasty. The aim of this study was to decompose the complex three-dimensional micromotion at the head-neck junction into multiple fundamental modes, including three translational and three rotational components. A three-dimensional finite element model composed of head-neck junction, liner and acetabular cup with a typical 12/14 taper size, as well as the taper mismatch of -4', was developed during walking. The analysis was divided into three procedures: a) the assembly simulation of the head and neck during surgery, b) verification with a simplified axisymmetric model, and c) three-dimensional modelling under normal walking. This study revealed that the main forms of micromotion contained circumferential, longitudinal micromotion and longitudinal rolling toggling, and were closely related to the state of motion. The maximum translational micromotion was predicted to be 10.9 µm during the walking gait, with the predominant modes of the circumferential translation of 9.6 µm, the longitudinal translation of 5.5 µm and the longitudinal rotation of 0.29° along the taper junction. These findings may provide design considerations for further experimental testing about fretting and facilitate the understanding of the fretting mechanisms in hip prostheses.

Video-urodynamics efficacy of sacral neuromodulation for neurogenic bladder guided by three-dimensional imaging CT and C-arm fluoroscopy: a single-center prospective study.

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the conversion rate from period I to period II, as well as the treatment efficiency and the occurrence of adverse events during the testing and follow-up phases. The testing phase of 52 NB patients was 18-60 days, with an average of (29.3 ± 8.0) days. Overall, 38 patients underwent SNM permanent electrode implantation, whose follow-up phase was 3-25 months, with an average of (11.9 ± 6.1) months. Compared with baseline, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased significantly in the testing phase. The daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased significantly in the testing phase. Besides, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased further from the testing to follow-up phase. Daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased further from testing to follow-up. At baseline, 10 ureteral units had vesicoureteral reflux (VUR), and 9 of them improved in the testing phase. Besides, there was 1 unit that further improved to no reflux during the follow-up phase. At baseline, 10 patients had detrusor overactivity (DO), and 8 of them improved in the testing phase. Besides, 1 patient's symptoms further improved during the follow-up phase. At baseline, there were 35 patients with detrusor-bladder neck dyssynergia (DBND); 14 (40.0%) of them disappeared during the testing phase. Among 13 cases who had DBND in the testing phase, 6 (46.2%) disappeared during the follow-up phase. Of the 47 patients with detrusor-external sphincter dyssynergia (DESD) at baseline, 8 (17.0%) disappeared during the testing phase. Among 26 cases who had DESD in the testing phase, 6 (23.1%) disappeared during the follow-up phase. The effective rate of this study was 88.5% (46/52), and the conversion rate from phase I to phase II was 73.1% (38/52). Additionally, the efficacy in a short-term follow-up was stable. SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy is an effective and safe treatment option for NB in short time follow-up. It would be well improved in the bladder storage function, sphincter synergetic function and emptying efficiency by video-urodynamics examination in this study.Trial registration: Chinese Clinical Trial Registry. ChiCTR2100050290. Registered August 25 2021. http://www.chictr.org.cn/index.aspx .

Generation and Release of OH Radicals from the Reaction of H2 O with O2 over Soot.

OH radicals in the air maintain the oxidizing power of the troposphere. A conventional view is that particulate matter (PM) in the atmosphere is a major sink of OH radicals, thereby lowering the oxidizing power of atmosphere in the event of high-level PM. By contrary, our joint experimental/theoretical study reveals a new mechanism for the generation of gaseous OH radicals by carbonaceous soot particles. We show that water and O2 react on carbonaceous surfaces and give rise to gaseous OH radicals under irradiation. With ample delocalized π electrons, carbonaceous surfaces enable the easy desorption of hydroxyl groups to produce gaseous OH radicals, evidenced by direct observation of the steady generation of OH radicals on a carbonaceous surface. Our results reveal a new chemical mechanism for the production of OH radicals.

Circular RNA Plasmacytoma Variant Translocation 1 (CircPVT1) knockdown ameliorates hypoxia-induced bladder fibrosis by regulating the miR-203/Suppressor of Cytokine Signaling 3 (SOCS3) signaling axis.

The effects of circular RNAs (circRNAs) on bladder outlet obstruction (BOO)-induced hypertrophy and fibrogenesis in rats and hypoxia-induced bladder smooth muscle cell (BSMC) fibrosis remain unclear. This study aimed to determine the regulatory role of circRNAs in the phenotypic changes in BSMCs in BOO-induced rats.circRNAmicroarray and real-time PCR were used to explore differentiated expressed circRNAs. Bioinformatics analyses and dual-luciferase reporter were performed to identify the targets for circRNA PVT1 (circPVT1). BOO was performed to establish a bladder fibrosis animal model. The circPVT1 and suppressor of cytokine signaling 3 (SOCS3) expression levels were upregulated (p = 0.0061 and 0.0328, respectively), whereas the microRNA-203a (miR-203) level was downregulated in rats with bladder remodeling (p=0.0085). Bioinformatics analyses and dual-luciferase reporter assay results confirmed that circPVT1 sponges miR-203 and that the latter targets the 3'-untranslated region of SOCS3. Additionally, circPVT1 knockdown alleviated BOO-induced bladder hypertrophy and fibrogenesis. Furthermore, hypoxia was induced in BSMCs to establish a cell model of bladder fibrosis. Hypoxia induction in BSMCs resulted in upregulated circPVT1 and SOCS3 levels (p = 0.0052) and downregulated miR-203 levels. Transfection with circPVT1 and SOCS3 shRNA ameliorated hypoxia-induced transforming growth factor-ß (TGF-ß1), TGFßR1, α-smooth muscle actin, fibrotic growth factor, extracellular matrix subtypes, BSMC proliferation, and apoptosis-associated cell injury, whereas co-transfection with miR-203 inhibitor counteracted the effect of circPVT1 shRNA on these phenotypes.These findings revealed a novel circRNA regulator of BOO-associated bladder wall remodeling and hypoxia-induced phenotypic changes in BMSCs by targeting the miR-203-SOCS3 signaling axis.

Apigenin Nanoparticle Attenuates Renal Ischemia/Reperfusion Inflammatory Injury by Regulation of miR-140-5p/CXCL12/NF-κB Signaling Pathway.

Apigenin as a natural flavonoid product has been proved previously to play a renoprotective effect during ischemia/reperfusion injury (IRI), but the particular mechanisms involving the positive effects of apigenin remain totally unclear. The study investigated apigenin's roles and underlying biological mechanisms in IR-induced acute kidney injury (AKI). Thirty-six mice received a right nephrectomy and clamping of the left renal artery for 30 minutes, and then perfusion for 24 h. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle) to enhance its bioavailability. Mice were subjected to intraperitoneally injection with apigenin (5, 10 or 20 mg/kg) for 24 h before surgery. For in vitro experiments, mouse renal tubular epithelial cells (mRTECs) and miR-140-5p mimic/inhibitor transfected mRTECs were subjected to hypoxia/reoxygenation in the presence or absence of apigenin. In vitro, we uncovered that hypoxia/reoxygenation stimulation caused inflammatory injury in mRTECs. Apigenin reduced the hypoxia/reoxygenation-induced cell inflammatory injury and NF- B p65 nuclear translocation from cytoplasm and activation. Moreover, apigenin reduced hypoxia/reoxygenationtriggered miR-140-5p down-regulation. What's more, the luciferase reporter system revealed that miR-140-5p negatively regulates CXCL12, which is its direct target of action. CXCL12 exhibited an inhibitory effect on the apigenin-induced inactivation of NF- B signaling pathway. Furthermore, we observed that apigenin pretreatment attenuated the IR-triggered up-regulation of serum creatinine and blood urea nitrogen, elevation of pro-inflammatory cytokines secretion and tubular cell apoptosis, enhancement of CXCL12 and decline of miR-140-5p in vivo. Our studies show that apigenin protects against IR-triggered renal cell inflammatory injury in vivo and in vitro by miR-140-5p up-regulation and CXCL12 downregulation via quenching the NF- B pathway activation. Apigenin may be an encouraging therapeutic agent for patients with IR-associated kidney injury.

Synthesis of poly(amide-thioether) with tunable hydrophilicity via thiolactone chemistry and its application in oil-in-oil emulsions.

Oil-in-oil emulsions are ideal systems for water-sensitive reactions such as polymerizations and catalytic reactions, which has received extensive attention in recent years. The application of oil-in-oil emulsions has been developed slowly due to the limited types of surfactants and complicated synthesis process. Herein, we proposed a simple method to prepare poly(amide-thioether)-based surfactant for oil-in-oil emulsions via taking advantage of single-pot multicomponent and click characters of thiolactone chemistry. Using a combination of alkyl amine and acrylamide thiolactone, the aminolysis of thiolctone occurred first, generating thiol group in-situ, and then the generated thiol group would sequentially react with the double bonds of acrylamide to form polythioether in the presence of amine. The hydrophobicity of the surfactant could be effectively adjusted by the chain length of the alkyl amine and thus this polymer could serve as a promising surfactant for oil-in-oil emulsion. Notably, the emulsion types could be switched by changing the chain length of the alkyl amine. In addition, the effects of surfactant loading, volume ratio of oil phases, oil types on the size and stability of oil-in-oil emulsions were further investigated. It was demonstrated that the oil-in-oil emulsion stabilized by poly(amide-thioether)s kept stable after more than five months. Besides, we preliminarily explored the application of the oil-in-oil emulsion to prepare closed cell foam and porous particles via photo-initiated thiol-ene polymerization. It is believed that this super-stable oil-in-oil emulsion could offer more possibilities for highly potential water-sensitive systems.

Utility of the EORTC risk tables and CUETO scoring model for predicting recurrence and progression in non-muscle-invasive bladder cancer patients treated with routine second transurethral resection.

PURPOSE: Routine second transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC) is common practice in Germany. Applicability of European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) models in NMIBC patients is still controversial. Aim of the study was to assess the performance of EORTC and CUETO predictive models in NMIBC patients treated with second TUR. METHODS: 479 NMIBC patients with routine second TUR were analyzed retrospectively between 2003 and 2011, and investigated with clinical and pathological variables in regard to tumor recurrence and progression. Furthermore, recurrencefree survival (RFS) and progression-free survival (PFS) were evaluated according to EORTC and CUETO, and the discrimination of the models assessed. RESULTS: With a median follow-up of 60 months, prior recurrence rate, grade, and second TUR pathology were independent prognostic factors for the risk of disease recurrence and progression. The concordance index of the EORTC and the CUETO model was 0.563 and 0.516 for recurrence and 0.681 and 0.702 for progression, respectively. The positive pathology after second TUR was significantly associated with risk of disease recurrence and progression. EORTC and CUETO risk models estimated progression better than recurrence, especially with higherscore groups. CONCLUSIONS: Improved predictive tools should be developed for optimal treatment selection.

Long noncoding RNA PCA3 regulates prostate cancer through sponging miR-218-5p and modulating high mobility group box 1.

OBJECTIVE: The purpose of this study was to investigate the mechanism of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in prostate cancer (PCa) via regulating the miR-218-5p/high mobility group box 1 (HMGB1) axis. METHODS: The Cancer Genome Atlas database was used to divide differentially expressed lncRNAs, microRNAs, and messenger RNA (mRNAs). The mRNA expressions of lncRNA PCA3, miR-218-5p, and HMGB1 were determined by reverse transcription polymerase chain reaction. Cell propagation was evaluated using the Cell Counting Kit-8 assay and the apoptotic rate was examined by flow cytometry. Cell migration and invasion were observed through the wound healing assay and transwell assay. Target relationships among PCA3, miR-218-5p, and HMGB1 were validated via dual-luciferase reporter gene assay. A nude mouse model in vivo was designed to evaluate the effect of PCA3 on prostate tumor growth. RESULTS: PCA3 and HMGB1 were high-expressed in PCa, whereas miR-218-5p was low-expressed. PCA3 knockdown or miR-218-5p overexpression suppressed PCa cell proliferation, migration, and invasion, but promoted apoptosis. Besides, targeted relationships and interactions on the expression between miR-218-5p and PCA3 or HMGB1 were elucidated. PCA3 weakened cell viability and mobility whereas induced apoptosis through binding with miR-218-5p. Meanwhile, miR-218-5p also inhibited PCa tumorigenesis via downregulation of HMGB1. Knockdown of PCA3 impeded tumor growth by downregulating its downstream gene HMGB1. CONCLUSIONS: lncRNA PCA3 facilitated PCa progression through sponging miR-218-5p and regulating HMGB1.

Synthesis and biological evaluation of novel alkyl diamine linked bivalent ß-carbolines as angiogenesis inhibitors.

We have synthesized and evaluated a series of novel alkyl diamine linked bivalent ß-carbolines as potent angiogenesis inhibitors. The results demonstrated that most bivalent ß-carbolines exhibited significant antiproliferative effects against human umbilical vein cell lines EA.HY926. Compound 4m was found to be the most potent antiproliferative agent with IC50 value of 2.16 µM against EA.HY926 cell lines. Mechanism investigations revealed that compound 4m could significantly inhibit EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover, compound 4m also showed obvious angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was more potent than the reference drug Endostar. The bivalent ß-carbolines might be served as candidates for the development of vascular targeting antitumor drugs.

High-grade Carcinoma of the Proximal Ureter With Negative Nephroureteroscopy Detected by a Positive FISH Test: A Rare Case Report.

Upper tract urothelial carcinomas in the proximal ureter are an uncommon disease. We present a case in which it was firstly detected by fluorescence in situ hybridization and not by endoscopy and radiologic imaging. Consequently, a radical nephroureterectomy with excision of the bladder cuff was performed as the gold standard treatment.

Exogenous calcium alleviates low night temperature stress on the photosynthetic apparatus of tomato leaves.

The effect of exogenous CaCl2 on photosystem I and II (PSI and PSII) activities, cyclic electron flow (CEF), and proton motive force of tomato leaves under low night temperature (LNT) was investigated. LNT stress decreased the net photosynthetic rate (Pn), effective quantum yield of PSII [Y(II)], and photochemical quenching (qP), whereas CaCl2 pretreatment improved Pn, Y(II), and qP under LNT stress. LNT stress significantly increased the non-regulatory quantum yield of energy dissipation [Y(NO)], whereas CaCl2 alleviated this increase. Exogenous Ca2+ enhanced stimulation of CEF by LNT stress. Inhibition of oxidized PQ pools caused by LNT stress was alleviated by CaCl2 pretreatment. LNT stress reduced zeaxanthin formation and ATPase activity, but CaCl2 pretreatment reversed both of these effects. LNT stress caused excess formation of a proton gradient across the thylakoid membrane, whereas CaCl2 pretreatment decreased the said factor under LNT. Thus, our results showed that photoinhibition of LNT-stressed plants could be alleviated by CaCl2 pretreatment. Our findings further revealed that this alleviation was mediated in part by improvements in carbon fixation capacity, PQ pools, linear and cyclic electron transports, xanthophyll cycles, and ATPase activity.

Synthesis and structure--activity relationships of N²-alkylated quaternary ß-carbolines as novel antitumor agents.

A series of novel N(2)-alkylated quaternary ß-carbolines was synthesized by modification of position-1, 2, 7 and 9 of ß-carboline nucleus with various alkyl and arylated alkyl substituents, and their cytotoxic activities in vitro and antitumor potencies in mice were evaluated. Compound 3m was found to be the most potent antitumor agent. SARs analysis revealed that (1) the substituents in position-2 and 9 of ß-carboline nucleus played a vital role in modulation of antitumor activity; (2) the benzyl and 3-phenylpropyl substituents in position-2 and 9 of ß-carboline ring were the optimal substituents giving rise to significant antitumor agent. These compounds might be a novel promising class of antitumor agents with clinical development potential.

Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents.

Harmine, a naturally occurring ß-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of ß-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure-activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities.

Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent ß-carbolines.

A series of bivalent ß-carbolines with a spacer of three to ten methylene units between the indole nitrogen was synthesized and evaluated as antitumor agents. The results demonstrated that compounds 18c, 21b, 25a and 31b exhibited strong cytotoxic activities with IC(50) value of lower than 20 µM against four tumor cell lines. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 18b, 21b, 26a and 31b exhibited potent antitumor activities with tumor inhibition rate of over 40% in animal models. Preliminary structure-activity relationships analysis indicated that (1) the spacer length affected antitumor potencies, and four to six methylene units were more favorable; (2) the introduction of appropriate substituent into position-1 of ß-carboline facilitated antitumor potencies.

[Flavectomy of cervical vertebrae in treating cervical spinal canal stenosis].

OBJECTIVE: To investigate the operational method of cervical vertebral flavectomy and its clinical application in the management of cervical canal stenosis. METHODS: From June 1997 to June 2007, 25 patients suffering from cervical spinal canal stenosis caused by obvious flaval ligament hypertrophy were given flavectomy. There were 22 males and 3 females, with an age range of 32 to 68 years (average 54 years). The course of disease was from 3 weeks to 7 years, with an average of 3 years and 7 months. All patients had degenerative cervical canal stenosis; of them, 5 cases had a history of cervical injury 2 to 3 weeks before operation (3 cases of falling injury and 2 cases of traffic accident injury). The X-ray film, CT, and MRI examinations showed that the compression locations were C4-7 in 12 cases, C3-7 in 9 cases, C5-7 in 3 cases, and C6,7 in 1 case. Spinous process and vertebral lamella were exposed by central posterior approach. The insertions of flaval ligaments were cut off at the superior vertebral lamella border, then the starting points of which were cut down from the anterior side of the upper vertebral lamella at their inferior border after lifting up the flaval ligaments. The residual flaval ligaments in front of the vertebral lamella were scraped off by slope rongeur, the dura mater then could be seen to inflate from the intervertebral lamella space, showing the compression having been relieved. Twenty-five cases were all given posterior flavectomy. At 1 week to 3 months after operation, 12 patients received anterior cervical discectomy or vertebral gaining decompression with fusion by bone graft. RESULTS: The time for flavectomy was from 60 to 180 minutes, with an average of 95 minutes. The blood loss during operation was from 90 to 360 mL, with an average of 210 mL. The dura matters were lacerated by knife tips during operation with the cervical vertebrae in hyperflexion in 2 cases. Immediate suture and repair were performed and there were no postoperative cerebrospinal fluid leakage. All the incisions healed by first intension after operation. All of the 25 cases were followed up from 2 to 10 years, with an average of 3 years and 9 months. All patients had no complication of axial symptoms, and no restenosis at their operation site of cervical canal stenosis. The section area ratios of functional spinal canal to spinal cord were 1.12 +/- 0.07 before operation and 2.11 +/- 0.19 at 24 months after operation, showing significant difference (P < 0.05). The range of motion of cervical vertebrae was (39.4 +/- 3.2) degrees before operation and (42.1 +/- 2.9) degrees at 24 months after operation in 13 cases without anterior cervical discectomy fusion, showing no significant difference (P > 0.05); was (34.3 +/- 3.4) degrees before operation and (29.2 +/- 3.6) degrees at 24 months after operation in 12 cases with anterior cervical discectomy fusion, showing significant difference (P < 0.05). The bone graft achieved bony union 3-5 months after operation (average 3.8 months). The Japanese Orthopaedic Association (JOA) scores were 7.9 +/- 2.2 before operation and 15.6 +/- 1.4 at 24 months after operation, showing significant difference (P < 0.05), with an average improvement rate of 86.3%. CONCLUSION: Cervical flavectomy could relieve compression to spinal cord and nerves caused by the flaval ligament hypertrophy without damaging the normal integrality of bony canal, thus avoiding the complication of axial symptoms and so on which are encountered in open-door expansile cervical laminoplasty.