Interest of the POSPOM score in estimating postoperative complication risk after radical cystectomy.

INTRODUCTION: Identifying patients at risk after cystectomy for cancer is essential. The POSPOM score is a non-specific urological surgery score for estimating postoperative hospital mortality. This study sought to validate the POSPOM score for predicting postoperative morbidity and mortality after cystectomy. METHODS: The study retrospectively included all patients undergoing cystectomy for muscle-invasive or locally advanced bladder cancer between 2010 and 2019 in one center. The primary objective was validation of the POSPOM score for calculating severe postoperative morbidity [Clavien-Dindo (CDC)≥3] and 90-day mortality after cystectomy. Secondary objectives were comparison to other predictive scores [Charlson (CCI), ASA]. RESULTS: At 90days, out of 167 patients, 26% (n=44) had a CDC≥3 complication and 8.4% (n=14) had died. POSPOM correlated with the risk of death at 90days (P<0.001) and postoperative transfusion (P<0.01). Patients with CDC≥3 complications had higher CCI and POSPOM (median 6.5 vs. 5, P<0.01 and 6.49% vs. 5.58%, P=0.029, respectively). Patients who died postoperatively had higher CCI and POSPOM (median 8 vs. 6, P<0.001 and 23.9% vs. 5.58%, P<0.001, respectively). The prognostic value of the POSPOM score for predicting mortality appears better [AUC=0.886 (0.798-0.973)] compared with CCI [AUC=0.812 (0.710-0.915)] and ASA [AUC=0.739 (0.630-0.849)], but not for predicting morbidity. CONCLUSION: This study confirms the robustness of the POSPOM score for estimating mortality and its limitations for predicting postoperative morbidity.

Focused low-intensity pulsed ultrasound alleviates osteoarthritis via restoring impaired FUNDC1-mediated mitophagy.

Mitophagy is critical for maintaining proper cellular functions, and it contributes to the onset and progression of osteoarthritis (OA). A recent study showed that focused low-intensity pulsed ultrasound (FLIPUS) could activate mitophagy, but the molecular mechanism remains unclear. This study aimed to elucidate the chondroprotective effects of FLIPUS in OA and the regulatory effects on FUN14-domain containing 1 (FUNDC1-mediated mitophagy. In vitro, FLIPUS improved inflammatory response, anabolism, and catabolism in interleukin (IL)-1ß-induced OA chondrocytes. The chondroprotective effects of FLIPUS were attributed to promoting the expression of phosphoglycerate mutase 5 (PGAM5) and the dephosphorylation of FUNDC1 at serine 13 (Ser13), as well as promoting the mitophagy process. In vivo, FLIPUS reduced the cartilage degeneration and apoptosis and reversed the change of anabolic- and catabolic-related proteins in destabilized medial meniscus (DMM)-induced mouse model. Thus, the study indicates that FLIPUS exhibits a chondroprotective effect via activating impaired FUNDC1-mediated mitophagy.

Pancreatic Allograft Thrombosis: Implementation of the CPAT-Grading System in a Retrospective Series of Simultaneous Pancreas-Kidney Transplantation.

Pancreatic graft thrombosis (PAT) is a major surgical complication, potentially leading to graft loss. The recently proposed Cambridge Pancreas Allograft Thrombosis (CPAT) grading system provides diagnostic, prognostic and therapeutic recommendations. The aim of the present study was to retrospectively assess computed tomography angiography (CTA) examinations performed routinely in simultaneous pancreas-kidney (SPK) recipients to implement the CPAT grading system and to study its association with the recipients' outcomes. We retrospectively studied 319 SPK transplant recipients, who underwent a routine CTA within the first 7 postoperative days. Analysis of the CTA scans revealed PAT in 215 patients (106 grade 1, 85 grade 2, 24 grade 3), while 104 showed no signs. Demographic data of the patients with and without PAT (thrombosis and non-thrombosis group) were not significantly different, except for the higher number of male donors in the thrombosis group. Pancreatic graft survival was significantly shorter in the thrombosis group. Graft loss due to PAT was significantly associated with grade 2 and 3 thrombosis, while it did not differ for recipients with grade 0 or grade 1 thrombosis. In conclusion, the CPAT grading system was successfully implemented in a large series of SPK transplant recipients and proved applicable in clinical practice.

Facilitation of axonal transcriptome analysis with quantitative microfluidic devices.

Microfluidic chambers are powerful tools for studying axonal mRNA localization and translation in neurons. In addition to specific manipulation and measurements of axons, microfluidic chambers are used for collecting axonal materials to perform axonal transcriptome analysis. However, traditional bipartite and tripartite chambers have limitations either in purity or quantity of collected axons. Here, we improved the design of traditional chambers. Moreover, we developed two new quantitative chambers, multi-compartmental quantitative bipartite chamber (MQBC) and long quantitative tripartite chamber (LQTC). Compared with the traditional chambers, MQBC and LQTC could dramatically increase the efficiency in collecting axonal RNA. Finally, we applied these chambers to do comparative axon transcriptome analysis of different types of neurons. Thus, our newly designed quantitative chambers significantly improve axon collection efficiency and facilitate axonal transcriptome analysis.

A nomogram based on platelet-to-lymphocyte ratio for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy.

OBJECTIVE: To investigate the role of platelet-to-lymphocyte ratio (PLR) in complete pathological response (pCR) of breast cancer (BC) patients after neoadjuvant chemotherapy (NAC), as well as to establish and validate a nomogram for predicting pCR. METHODS: BC patients diagnosed and treated in the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to June 2022 were included. The correlation between pCR and clinicopathological characteristics was analyzed by Chi-square test. Logistic regression analysis was performed to evaluate the factors that might affect pCR. Based on the results of regression analysis, a nomogram for predicting pCR was established and validated. RESULTS: A total of 112 BC patients were included in this study. 50.89% of the patients acquired pCR after NAC. Chi-square test showed that PLR was significantly correlated with pCR (X2 = 18.878, P < 0.001). And the PLR before NAC in pCR group was lower than that in Non-pCR group (t = 3.290, P = 0.001). Logistic regression analysis suggested that white blood cell (WBC) [odds ratio (OR): 0.19, 95% confidence interval (CI): 0.04-0.85, P = 0.030)], platelet (PLT) (OR: 0.19, 95%CI: 0.04-0.85, P = 0.030), PLR (OR: 0.18, 95%CI: 0.04-0.90, P = 0.036) and tumor grade (OR: 9.24, 95%CI: 1.89-45.07, P = 0.006) were independent predictors of pCR after NAC. A nomogram prediction model based on WBC, PLR, PLR and tumor grade showed a good predictive ability. CONCLUSION: PLR, PLT, WBC and tumor grade were independent predictors of pCR in BC patients after NAC. The nomogram based on the above positive factors showed a good predictive ability.

Fabrication of Porous Tantalum with Low Elastic Modulus and Tunable Pore Size for Bone Repair.

Porous tantalum (Ta) is a potential bone substitute due to its excellent biocompatibility and desirable mechanical properties. In this work, a series of porous Ta materials with interconnected micropores and varying pore sizes from 23 to 210 µm were fabricated using spark plasma sintering. The porous structure was formed by thermal decomposition of ammonium bicarbonate powder premixed in the Ta powder. The pore size and porosity were controlled by the categorized particle size of ammonium bicarbonate. The porous Ta has elastic moduli in the range of 2.1-3.2 GPa and compressive yield strength in the range of 23-34 MPa, which are close to those of human bone. In vitro, as-fabricated porous Ta demonstrates excellent biocompatibility by supporting adhesion and proliferation of preosteoblasts. In vivo studies also validate its bone repair capability after implantation in a rat femur defect model. The study demonstrates a facile strategy to fabricate porous Ta with controllable pore size for bone repair.

Knockdown of RSPH14 inhibits proliferation, migration, and invasion and promotes apoptosis of hepatocellular carcinoma via RelA.

BACKGROUND: High RSPH14 expression appears to be related to poor prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the possible roles of RSPH14 in the proliferation, apoptosis, and invasion of HCC cells. METHODS: The UALCAN database and Kaplan-Meier Plotter were used to evaluate the expression level and prognostic role of RSPH14 in HCC. Lentiviral vectors containing shRNA against RSPH14 were constructed to transfect the BEL-7404 and SMMC-7721 HCC cell lines. Cell proliferation was investigated by BrdU, MTT, and colony-formation assays. Apoptosis was detected using flow cytometry. Cell migration and invasion were evaluated using the scratch wound-healing and Transwell assays. Immunohistochemistry and western blot were used to determine the expression levels of the proteins. The function of RSPH14 in vivo was evaluated using a xenograft mouse model. RESULTS: The expression of RSPH14 was higher in HCC tumor tissues than in adjacent normal tissues and was closely related to unfavorable prognostic factors and poorer survival (all P < 0.05). Knockdown of RSPH14 inhibited the cell proliferation, migration, and invasion of HCC cells and promoted apoptosis (all P < 0.05). Knockdown of RSPH14 inhibited tumor growth in vivo (P < 0.05). RSPH14 knockdown led to decreased expression of RelA (NF-κBp65), CDH2, and AKT1, thereby affecting the functions of the HCC cells (all P < 0.05). RelA overexpression could abate the inhibitory effect of BEL-7404 cell proliferation caused by RSPH14 depletion. CONCLUSION: Knockdown of RSPH14 could decrease cell proliferation, migration, and invasion and increase apoptosis of HCC cells by inhibiting RelA expression. RSPH14 could be a new treatment target for HCC.

The Synergy of Topographical Micropatterning and Ta|TaCu Bilayered Thin Film on Titanium Implants Enables Dual-Functions of Enhanced Osteogenesis and Anti-Infection.

Poor osteogenesis and implant-associated infection are the two leading causes of failure for dental and orthopedic implants. Surface design with enhanced osteogenesis often fails in antibacterial activity, or vice versa. Herein, a surface design strategy, which overcomes this trade-off via the synergistic effects of topographical micropatterning and a bilayered nanostructured metallic thin film is presented. A specific microgrooved pattern is fabricated on the titanium surface, followed by sequential deposition of a nanostructured copper (Cu)-containing tantalum (Ta) (TaCu) layer and a pure Ta cap layer. The microgrooved patterns coupled with the nanorough Ta cap layer shows strong contact guidance to preosteoblasts and significantly enhances the osteogenic differentiation in vitro, while the controlled local sustained release of Cu ions is responsible for high antibacterial activity. Importantly, rat calvarial defect models in vivo further confirm that the synergy of microgrooved patterns and the Ta|TaCu bilayered thin film on titanium surface could effectively promote bone regeneration. The present effective and versatile surface design strategy provides significant insight into intelligent surface engineering that can control biological response at the site of healing in dental and orthopedic implants.

Engineering High-Resolution Micropatterns Directly onto Titanium with Optimized Contact Guidance to Promote Osteogenic Differentiation and Bone Regeneration.

Topographical cues play an important role in directing cell behavior, and thus, extensive research efforts have been devoted to fabrication of surface patterns and exploring the contact guidance effect. However, engineering high-resolution micropatterns directly onto metallic implants remains a grand challenge. Moreover, there still lacks evidence that allows translation of in vitro screening to in vivo tissue response. Herein, we demonstrate a fast, cost-effective, and feasible approach to the precise fabrication of shape- and size-controlled micropatterns on titanium substrates using a combination of photolithography and inductively coupled plasma-based dry etching. A titanium TopoChip containing 34 microgrooved patterns with varying geometry parameters and a flat surface as the control was designed for a high-throughput in vitro study of the contact guidance of osteoblasts. The correlation between the surface pattern dimensions, cell morphological characteristics, proliferation, and osteogenic marker expression was systematically investigated in vitro. Furthermore, the surface with the highest osteogenic potential in vitro along with representative controls was evaluated in rat cranial defect models. The results show that microgrooved pattern parameters have almost no effect on osteoblast proliferation but significantly regulate the cell morphology, orientation, focal adhesion (FA) formation, and osteogenic differentiation in vitro. In particular, a specific groove pattern with a ridge width of 3 µm, groove width of 7 µm, and depth of 2 µm can most effectively align the cells through regulating the distribution of FAs, resulting in an anisotropic actin cytoskeleton, and thereby promoting osteogenic differentiation. In vivo, microcomputed tomography and histological analyses show that the optimized pattern can apparently stimulate new bone formation. This study not only offers a microfabrication method that can be extended to fabricate various shape- and size-controlled micropatterns on titanium alloys but also provides insight into the surface structure design of orthopedic and dental implants for enhanced bone regeneration.

Cancellous-Bone-like Porous Iron Scaffold Coated with Strontium Incorporated Octacalcium Phosphate Nanowhiskers for Bone Regeneration.

The repair of large bone defects poses a grand challenge in tissue engineering. Thus, developing biocompatible scaffolds with mechanical and structural similarity to human cancellous bone is in great demand. Herein, we fabricated a three-dimensional (3D) porous iron (Fe) scaffold with interconnected pores via a template-assisted electrodeposition method. The porous Fe scaffold with a skeleton diameter of 143 µm had the porosity >90%, an average pore size of 345 µm, and a yield strength of 3.5 MPa. Such structure and mechanical strength were close to those of cancellous bone. In order to enhance the biocompatibility of the scaffold, strontium incorporated octacalcium phosphate (Sr-OCP) was coated on the skeletons of the porous Fe scaffold. The coated Sr-OCP was in the form of nanowhiskers with a mean diameter of 300 nm and length of 30 µm. Such Sr-OCP coating could effectively reduce the release rate of the Fe ions to a level which was safe for the human body. Both in vitro cytotoxicity tests by extraction method and direct contact assay confirmed that the Sr-OCP coating could promote the cell adhesion and substantially enhance the biocompatibility of the porous Fe scaffolds. Thus, the cancellous-bone-like porous structure with compatible mechanical properties and excellent biocompatibility enables the present Sr-OCP coated porous Fe scaffold to be a promising candidate for bone repair and regeneration.

Effectiveness and Complications of the AMS AdVance™ Male Sling System for the Treatment of Stress Urinary Incontinence: A Prospective Multicenter Study.

OBJECTIVE: To evaluate the effectiveness and tolerance of the AdVance Male Sling System for the treatment of male stress urinary incontinence in patients after prostatic surgery. METHODS: An international, observational, prospective, multicenter study was conducted on male patients with urinary incontinence after prostatic surgery. Patients underwent a 24-hour pad test with a threshold at 250 g. All patients were operated with the same AdVance implant procedure. They were seen 6 weeks later, and examined again at 3, 6, 12, and 24 months. Incontinence was measured using 1-hour and 24-hour pad tests, the number of protective pads used, ICIQ-SF and IQoL questionnaires. Success was defined as no urinary leakage and no pad use. Patient improvement was defined as a reduction of more than 50% in leakage and no more than one pad used per day. Any perioperative and late complications were documented. RESULTS: From January 2007 to November 2012, 113 patients were successfully operated on. At 24 months after surgery, the mean weight of the 1-hour pad test had decreased from 48.7 g to 6.6 g (P < 0.001) while that of the 24-hour pad test decreased to 45.0 g from 113.9 g (P < 0.001). Success and improvement occurred in 22.6% and 58.0% of the patients, respectively. Seventy-five patients (80.6%) used none or one protective pad daily, and the IQoL and ICIQ-SF scores were both significantly improved. Fourteen patients (12.4%) required a second intervention. Three patients (2.7%) had a Clavien IIIb complication. CONCLUSION: The AdVance Male Sling System is an effective treatment for mild to moderate male stress urinary incontinence. Complications from its use are rare and 24-month results are satisfactory.

Visible-light-controllable drug release from multilayer-coated microneedles.

A method for the generation of visible-light-controllable drug release polyelectrolyte multilayers on poly(l-lactide) (PLLA) microneedles is developed by host-guest chemistry. In response to visible light irradiation, model drugs encapsulated on polyelectrolyte multilayers transfer into the skin following brief microneedle application.

Clinical-psychological characteristics of refractory globus patients in China.

BACKGROUND: Refractory globus is not rare in clinical practice, but little research about it. AIMS: To investigate the clinical-psychological characteristics of patients with refractory globus. METHODS: Six hundred and nineteen globus patients were divided into the refractory globus group (n=149) and the non-refractory globus group (n=470). All subjects completed the following questionnaires: demographic characteristics, medical information, Hamilton Rating Scale of Anxiety/Depression, Pittsburgh Sleep Quality Index, Glasgow Edinburgh Throat Scale, and 36-item Short Form Health Survey. RESULTS: No significantly differences were found in demographic characteristics between the two groups, but the refractory globus group had longer disease duration and more serious symptoms. Sought healthcare more frequently but still had poorer quality of life than did the non-refractory globus group. Compared with the non-refractory globus group, the refractory globus group also had higher percentages of anxiety, depression, and sleep disorders. Positive correlations were observed between the severity of globus symptoms and HAMA, HAMD, and PSQI scores. CONCLUSIONS: Refractory globus is not rare in clinical practice and should receive more attention from patients and doctors because of its severe symptoms, long disease duration, poor quality of life, and accompanied by psychological disorders and sleep disorders.

Distribution profiles of transient receptor potential melastatin- and vanilloid-related channels in rat spermatogenic cells and sperm.

In the present study, we aimed to investigate the expression and distribution of transient receptor potential melastatin (TRPM)- and vanilloid (TRPV)- related channels in rat spermatogenic cells and spermatozoa. Spermatogenic cells and spermatozoa were obtained from male Sprague-Dawley rats. Reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of all TRPM and TRPV channel members with specific primers. Western blot analysis was applied for detecting the expression of TRPM and TRPV channel proteins. Immunohistochemistry staining for TRPM4, TRPM7 and TRPV5 was also performed in rat testis. The mRNAs of TRPM3, TRPM4, TRPM7 and TRPV5 were detected in the spermatogenic cells and spermatozoa in rat. Western blot analysis verified the expression of TRPM4, TRPM7 and TRPV5 in the rat spermatogenic cells and spermatozoa. Immunocytochemistry staining for TRPM and TRPV channel families indicated that TRPM4 and TRPM7 proteins were highly expressed in different stages of spermatogenic cells and spermatozoa, while TRPV5 protein was lowly expressed in these cells. Our results demonstrate that mRNAs or proteins for TRPM3, TRPM4, TRPM7 and TRPV5 exist in rat spermatogenic cells and spermatozoa. These data presented here may assist in elucidating the possible physiological function of TRPM and TRPV channels in spermatogenic cells and spermatozoa.