Effect of bladder emptying status on the ureteral access sheath insertion resistance and following ureteral injury in RIRS: a prospective randomized controlled trial in academic hospital.

PURPOSE: To evaluate the effect of bladder emptying status on the ureteral access sheath (UAS) insertion resistance and following ureteral injury. METHODS: Eighty patients were enrolled and randomly divided into bladder emptying group and control group before UAS placement. A digital force gauge (Imada Z2-50N) was used to measure the resistance during the UAS insertion. The ureteral injury was evaluated and graded with Post-Ureteroscopic Lesion Scale (PULS) system at the end of procedure. The mean resistance, maximum resistance in different ureteral segments, and ureteral injury were compared between the two groups. RESULTS: The mean resistance (3.12 ± 0.49 vs. 4.28 ± 0.52 N, P < 0.001), maximum resistance in the whole procedure (5.17 ± 0.72 vs. 6.39 ± 0.96 N, P < 0.001) and distal ureter (3.07 ± 0.75 vs. 6.18 ± 1.17 N, P < 0.001) in the bladder emptying group were significantly lower when compared to the control group. In subgroup analysis, the similar result was also noted in patients with BMI ≥ 25 when compared to patients with BMI < 25, while there was no significant difference between men and women, age ≥ 50 years versus age < 50 years. The incidence of PULS 1-2 ureteral injury in the bladder emptying group was lower than the control group (35% vs. 55%, P = 0.045). The ureteral injury in distal ureteral was less frequently noted in bladder emptying group than the control group (22.5% vs. 55%, P = 0.006); however, there was no significant difference in middle and upper ureter (P > 0.05). CONCLUSION: Emptying the bladder before UAS insertion can effectively reduce the UAS insertion resistance and the risk of distal ureteral injury in RIRS.

Development and internal validation of a prediction model to evaluate the risk of severe hemorrhage following mini-percutaneous nephrolithotomy.

PURPOSE: To develop a new prediction model for assessing the severe hemorrhage events in post mini-percutaneous nephrolithotomy (mini-PCNL) patients and internally validate it, thus to guide decision making in clinical practice. METHODS: The patients who underwent mini-PCNL were retrospectively reviewed. Potential risk factors were included as prediction variables for multivariate logistic regression analysis to identify independent risk factors, and prediction model was constructed. The predictive ability of the model was evaluated using the Concordance index (C-index) and Brier score. Bootstrapping resampling technique was used to perform internal validation. The related packages in R were used to generate the web application based on the prediction model. RESULTS: Multiple-tract was the strongest predictor of severe hemorrhage following mini-PCNL. Other risk factors were none or mild hydronephrosis, congenital anomalies of urinary system, urinary tract infection, operation time and stone peak Hounsfield unit. A prediction model was constructed to assess the probability of severe hemorrhage after mini-PCNL. The C-index and Brier score were 0.731 and 0.093, respectively after correcting for optimism, which signified the excellent discrimination and calibration. CONCLUSION: A new prediction model was developed to estimate risk of severe hemorrhage after mini-PCNL. It had been internally validated with good discrimination and calibration. The prediction model might be beneficial for endourologists in surgical decision-making and risk aversion.

Recent Progress of Tactile and Force Sensors for Human-Machine Interaction.

Human-Machine Interface (HMI) plays a key role in the interaction between people and machines, which allows people to easily and intuitively control the machine and immersively experience the virtual world of the meta-universe by virtual reality/augmented reality (VR/AR) technology. Currently, wearable skin-integrated tactile and force sensors are widely used in immersive human-machine interactions due to their ultra-thin, ultra-soft, conformal characteristics. In this paper, the recent progress of tactile and force sensors used in HMI are reviewed, including piezoresistive, capacitive, piezoelectric, triboelectric, and other sensors. Then, this paper discusses how to improve the performance of tactile and force sensors for HMI. Next, this paper summarizes the HMI for dexterous robotic manipulation and VR/AR applications. Finally, this paper summarizes and proposes the future development trend of HMI.

Microfluidic chip-based long-term preservation and culture of engineering bacteria for DNA damage evaluation.

Understanding the effects of long-term exposure to space environment is paramount to maintaining the safety, health of astronauts. The physical dosimeters currently used on the space station cannot be used to assess the physiological effects of radiation. Moreover, some developed biological methods are time-consuming and passive and cannot be used for active and real-time detection of the physiological effects of radiation in space environment. Here, the SOS promoter: recA-eGFP genetic engineering bacteria was constructed and characterized, and DNA damage effects of some chemical reagents and radiation were evaluated. The results indicated the constructed engineering bacteria can distinguish DNA damage reagents from non-damage reagents and have a good dose-fluorescence effect against Co-60 radiation with the detection limit of 0.64 Gy; in order to overcome the restriction of long-term preservation of bacteria in space environment, the bacteria were freeze-dried, and the protectants were optimized, the storage time of bacteria under dry conditions was explored by accelerated storage experiment. Finally, a microfluidic chip was designed and fabricated for freeze-drying genetic engineering bacteria recovery, culture, and analysis in space environment. This study can provide support for the establishment of on-orbit radiation damage risk monitoring and early warning and can provide basic data for maintaining the health and performance of astronauts on long-term space flight missions. Moreover, the technique developed herein has a great potential to be used as a powerful tool for efficiently screening various radioactive substance, toxic chemicals, drugs, etc. KEY POINTS: • The SOS promoter: recA-eGFP genetic engineering bacteria was successfully constructed, which can distinguish DNA damage reagents from non-damage reagents and possess a good dose-effect relationship against Co-60 radiation. • The bacteria were freeze-dried to overcome the restriction of long-term preservation of bacteria in space environment, and protectants were optimized, and the survival rate of freeze-dried engineering bacteria can be predicted based on the results of accelerated storage experiment. • Microfluidic chip-based culture platform was successfully designed, fabricated, and used for freeze-drying genetic engineering bacteria recovery, culture, and analysis.

Activated mitochondrial apoptosis in hESCs after dissociation involving the PKA/p-p53/Bax signaling pathway.

Human embryonic stem cells (hESCs) are highly fragile with massive cell death after dissociation into single cells, which seriously hampers their applications. The mechanism underlying the massive cell death after dissociation still remains elusive. Here, the expression of apoptosis-related proteins, cell survival and mitochondrial membrane potential in dissociated hESCs before and after the treatments with a protein kinase A (PKA) inhibitor H89 and p53 inhibitor Pifithrin α were investigated, respectively. Protein interactions were identified by immunoprecipitation and immunofluorescence. The results show that the dissociation causes Caspase-dependent apoptosis in hESCs mediated by mitochondrial pathway with the up-regulation of pro-apoptotic proteins, decrease in mitochondrial membrane potential and elevation in pro-apoptotic Cyto c release, which are obviously suppresses by H89. The dissociation-induced increase of phosphorylated p53 Ser15 (p-p53) is suppressed by Pifithrin α which also rescues the elevated levels of pro-apoptotic proteins in mitochondrial pathway. During the dissociation-induced apoptosis, PKA/p-p53/Bax signaling pathway is identified by immunoprecipitation and immunofluorescence showing the most likely interaction between them. These results indicate that dissociation induces mitochondrial apoptosis in hESCs involving PKA/p-p53/Bax signaling pathway, which not only give new insights into the apoptosis mechanism of dissociated hESCs, but also provide clues for developing potential strategies to promote hESC survival after dissociation.

Protein kinase A inhibitor, H89, enhances survival and clonogenicity of dissociated human embryonic stem cells through Rho-associated coiled-coil containing protein kinase (ROCK) inhibition.

STUDY QUESTION: Can cell survival of dissociated human embryonic stem cells (hESCs) be increased during culture? SUMMARY ANSWER: A protein kinase A (PKA) inhibitor, H89, can significantly enhance survival and clonogenicity of dissociated hESCs without affecting their pluripotency. WHAT IS KNOWN ALREADY: hESCs are vulnerable to massive cell death upon cellular detachment and dissociation. STUDY DESIGN, SIZE, DURATION: hESCs were dissociated into single cells and then cultured in feeder-dependent and -independent manners. H89 was added to the culture medium at different concentrations for 1 day. The statistical results were obtained from at least three independent experiments (n ≥ 4). The group without treatment was used as the negative control. PARTICIPANTS/MATERIALS, SETTING, METHODS: 4 µM H89 was added in the culture medium to promote cell survival and colony formation of dissociated hESCs. MTT method and propidium iodide (PI) staining were used to determine cell proliferation, cell death and cell cycle, respectively. To count colony formation, alkaline phosphatase (AP) staining was carried out. Western blot was performed to determine protein expression. Except AP staining, immunofluorescence, RT-PCR and karyotype analysis were used to confirm the pluripotent state of H89 treated hESCs. MAIN RESULTS AND THE ROLE OF CHANCE: H89 inhibits the dissociation-induced phosphorylation of PKA and two substrates of Rho-associated coiled-coil containing protein kinase (ROCK), myosin light chain (MLC2) and myosin phosphatase target subunit 1 (MYPT1), significantly increases cell survival and colony formation, and strongly depresses dissociation-induced cell death and cell blebbing without affecting the pluripotency of hESCs and their differentiation in vitro. LIMITATIONS, REASONS FOR CAUTION: Appropriate H89 concentration should be used and 1 day of H89 treatment is sufficient for promoting survival and colony formation of dissociated hESCs. WIDER IMPLICATIONS OF THE FINDINGS: These results provide an alternative for human pluripotent stem cell (hPSC) culture, broaden the scope of participants in the cell death of single hES cells after dissociation and further enlighten clues to understand the mechanism of dissociation-induced cell death. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Natural Science Foundation of China (21176238, 21576266), and Chinese Academy of Sciences. There is no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Nil.

Sensitivity of human embryonic stem cells to different conditions during cryopreservation.

Low cell recovery rate of human embryonic stem cells (hESCs) resulting from cryopreservation damages leads to the difficulty in their successful commercialization of clinical applications. Hence in this study, sensitivity of human embryonic stem cells (hESCs) to different cooling rates, ice seeding and cryoprotective agent (CPA) types was compared and cell viability and recovery after cryopreservation under different cooling conditions were assessed. Both extracellular and intracellular ice formation were observed. Reactive oxidative species (ROS) accumulation of hESCs was determined. Cryopreservation of hESCs at 1 °C/min with the ice seeding and at the theoretically predicted optimal cooling rate (TPOCR) led to lower level of intracellular ROS, and prevented irregular and big ice clump formation compared with cryopreservation at 1 °C/min. This strategy further resulted in a significant increase in the hESC recovery when glycerol and 1,2-propanediol were used as the CPAs, but no increase for Me2SO. hESCs after cryopreservation under all the tested conditions still maintained their pluripotency. Our results provide guidance for improving the hESC cryopreservation recovery through the combination of CPA type, cooling rate and ice seeding.

Membrane permeability of the human pluripotent stem cells to Me2SO, glycerol and 1,2-propanediol.

Due to the unlimited capacity of self-renew and ability to differentiate into derivatives of three germ layers, human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have a great potential in regenerative medicine. A major challenge we are facing during the long-term storage of human pluripotent stem cells with the conventional slow cooling rate is the low cell recovery rate after cryopreservation which cannot meet the requirements for the future clinical applications. Evaluating the cell membrane permeability and the corresponding activation energy of hESCs and hiPSCs for water and different cryoprotective agents (CPA), including dimethyl sulfoxide (Me2SO), 1,2-propandiol and glycerol, is important for facilitating the development of cryopreservation protocol to enhance cell recovery after the cryopreservation. The osmotically inactive volume of hESCs and hiPSCs determined using the Boyle-van't Hoff model was 0.32V0 and 0.42V0, respectively. The membrane permeability was assessed from the volume changes of cells exposed to Me2SO, 1,2-propanediol and glycerol at the temperatures ranging from 8 to 30°C. These results showed the biophysical differences between hESCs and hiPSCs. Their activation energy for water and CPAs extrapolated from the Arrhenius relationship indicated that the water transport was probably not through the channel-mediated mechanism.

Lateral flow strip assay of a gene segment in the COVID-19 virus with combined dual readout mode and preliminary multisite hybrid chain reaction amplification.

The past and present scenario of COVID-19 has revealed the necessity of simple point-of-care tests. When combined with the great advantages of amplification, lateral flow assay nucleic acid analysis represents a more sensitive molecular diagnostic technique compared to universal protein analysis. Room temperature operation, an enzyme-free nature, and in situ elongation make hybrid chain reaction amplification (HCR) a good candidate for amplified combined lateral flow assays (LFAs). Since dual modes of detection can not only satisfy different application scenarios, but also reduce the false-negative rate, in this paper, visual and fluorescent detection based on labelling with colloidal gold nanoparticles and fluorescence labelling were incorporated into a HCR integrated with a LFA. The detection assay was finished in 30 minutes. The linear relationship between the signal and the concentration of the characteristic segment in the COVID-19 ORF gene was demonstrated. The obtained detection limits of as low as 10 fM (6.02 × 103 copies per mL) and 1 fM (6.02 × 102 copies per mL), respectively, were comparable with those in the literature. The multi-site HCR amplification integrated with LFA of a 1053 bp nucleic acid chain was also preliminarily studied, and tri-site amplification was found to exhibit higher signal intensity than single-site amplification. This study provides a promising strategy for simple, sensitive, and wide-ranging detection of pathogenic bacteria.

Recent Progress in Long-Term Sleep Monitoring Technology.

Sleep is an essential physiological activity, accounting for about one-third of our lives, which significantly impacts our memory, mood, health, and children's growth. Especially after the COVID-19 epidemic, sleep health issues have attracted more attention. In recent years, with the development of wearable electronic devices, there have been more and more studies, products, or solutions related to sleep monitoring. Many mature technologies, such as polysomnography, have been applied to clinical practice. However, it is urgent to develop wearable or non-contacting electronic devices suitable for household continuous sleep monitoring. This paper first introduces the basic knowledge of sleep and the significance of sleep monitoring. Then, according to the types of physiological signals monitored, this paper describes the research progress of bioelectrical signals, biomechanical signals, and biochemical signals used for sleep monitoring. However, it is not ideal to monitor the sleep quality for the whole night based on only one signal. Therefore, this paper reviews the research on multi-signal monitoring and introduces systematic sleep monitoring schemes. Finally, a conclusion and discussion of sleep monitoring are presented to propose potential future directions and prospects for sleep monitoring.

Translation and validation of the Chinese version of Wisconsin Stone Quality of Life questionnaire in patients with kidney stones.

BACKGROUND: Wisconsin Stone Quality of Life (WISQOL) has been designed specifically for patients with kidney stones. The present study aimed to develop the Chinese version of WISQOL and reach its validation. METHODS: The WISQOL was translated into Chinese following a standard procedure. Kidney stone patients admitted for surgical treatment were enrolled and fulfilled both WISQOL and SF-36 on the admission day and at one month postoperatively. The internal consistency, inter-domain correlation and convergent validity were analyzed. RESULTS: One hundred twenty-four 124 males and 76 females were enrolled. The total WISQOL Score and SF-36 had significant correlation both preoperatively (r=0.772, P<0.01) and postoperatively (r=0.639, P<0.01). The internal consistency of the Chinese version WISQOL's different domains ranged from 0.766 to 0.959. The value of Spearman rank correlation to assess the convergent validity of different domains ranged from 0.444 to 0.687. The postoperative WISQOL raised about 20% showing a better quality of life. CONCLUSIONS: The Chinese version of WISQOL questionnaire was a reliable tool to evaluate the health quality of life in Chinese-speaker patients with kidney stones. To evaluate its test-retest reliability, reliability and validity in a longer term, further studies are required.

Wearable Continuous Blood Pressure Monitoring Devices Based on Pulse Wave Transit Time and Pulse Arrival Time: A Review.

Continuous blood pressure (BP) monitoring is of great significance for the real-time monitoring and early prevention of cardiovascular diseases. Recently, wearable BP monitoring devices have made great progress in the development of daily BP monitoring because they adapt to long-term and high-comfort wear requirements. However, the research and development of wearable continuous BP monitoring devices still face great challenges such as obvious motion noise and slow dynamic response speeds. The pulse wave transit time method which is combined with photoplethysmography (PPG) waves and electrocardiogram (ECG) waves for continuous BP monitoring has received wide attention due to its advantages in terms of excellent dynamic response characteristics and high accuracy. Here, we review the recent state-of-art wearable continuous BP monitoring devices and related technology based on the pulse wave transit time; their measuring principles, design methods, preparation processes, and properties are analyzed in detail. In addition, the potential development directions and challenges of wearable continuous BP monitoring devices based on the pulse wave transit time method are discussed.

Fabrication of micro free-flow electrophoresis chip by photocurable monomer binding microfabrication technique for continuous separation of proteins and their numerical simulation.

In this study, a simple, fast, and reliable method to fabricate a micro free-flow electrophoresis (µFFE) device on glass is presented. The two-dimensional depth channel in the chip was easily achieved by using a photocurable monomer (NOA 81) that served as the bonding material. In such a geometrical structure (two-dimensional depth channel), the effect of fluid behavior on the separation efficiency of micro free-flow zone electrophoresis (µFFZE) was simulated. The results of numerical simulation indicate that the pressure at the inlets may play an important role in the separation performance. Under the optimum separation conditions, four FITC-labeled amino acids were well separated, indicating the validity of the performance of the chip. Since the chip was fabricated by organic polymer bonding, it was easily recyclable through a simple re-fabrication process. The reproducibility of results from these recycling re-fabrication chips was investigated. The RSD of the resolution between FITC-L-glycine and FITC-L-phenylalanine was 5.3%. Furthermore, three FITC-labeled proteins were successfully separated with the resolution of 2.2 and 5.46, respectively, by using the coating of neutral liposome.

Retrograde intrarenal surgery in lateral position for lower pole stone: an initial experience from Single Academic Hospital.

Retrograde intrarenal surgery (RIRS) was generally challenging in management of lower pole stone (LPS) since the unfavorable anatomy. Theoretically, LPS was prone to fall out and down to renal pelvis when patients turned to lateral position, thus to facilitate lithotripsy. The aim of the present study was to report our initial experience of RIRS in lateral position for LPS. From January 2020 to February 2021, 21 patients with LPS received RIRS in lateral position. The intraoperative finding, operation time, complications and stone-free rate (SFR) were recorded and analyzed. The mean stone size was 16.7 ± 2.4 mm, multiple stones in lower pole were noted in 38.1% (8/21) cases. The mean infundibular-pelvic angle (IPA) was 35.2 ± 6.9°, IPA less than 30° was noted in six cases (28.6%, 6/21). Mean operation time was 43.5 ± 6.3 min. Obvious stone fragments dropping from the lower calyx to renal pelvis during the lithotripsy were noted in 17 cases (81.0%). Only one case (4.8%) suffered postoperative fever (Clavien I), no severe complication (> Clavien II) was noted. Hospital stay was 1.1 ± 0.3 days, the SFR in postoperative 1 month was 85.7%. LPS was prone to fall out and down to renal pelvis when patients in lateral position, thus to facilitate the lithotripsy. RIRS in lateral position was feasible for the management of LPS; however, RCT with large sample was required to certify our initial finding.

Development of high-resolution multidimensional native protein microfluidic chip electrophoresis fingerprinting and its application in the quick analysis of unknown microorganisms.

The unascertained, constant mutation and emergence of new types of microorganisms present significant challenges to their detection. Differing from the focus on the limited local 16S rRNA gene or protein markers, characteristic whole fingerprint technologies at the omic level are particularly suitable for unknown analytes since accurate knowledge about the constituents is not necessarily required. Herein, through a combination of several innovative strategies, including pure water isotachophoresis integrated (2 + 1)D electrophoresis, inversion-funnel peak stacking channel geometry and COMSOL computer-aided fluid simulation, high-resolution whole protein 2D native microfluidic chip electrophoresis was achieved within less than 1 min. The highest ever reported peak capacity for native 2D chip electrophoresis was obtained. Furthermore, taking Escherichia coli, Staphylococcus aureus, and Bacillus subtilis as model analytes without protein biomarker information, the feasibility of the identification and semiqualification of unknown microbes in pure or mixed samples was explored with the utilisation of original algorithms, including SIFT feature abstraction and a global information entropy combined support vector machine. As such, the multidisciplinary cooperation in the present study demonstrates monstrated promising prospects for microfluidic chip electropherogram fingerprint-based quick microorganism assays, biointeraction studies, and drug screenings, even if the analytes are not fully ascertained.

Electrooculography and Tactile Perception Collaborative Interface for 3D Human-Machine Interaction.

The human-machine interface (HMI) previously relied on a single perception interface that cannot realize three-dimensional (3D) interaction and convenient and accurate interaction in multiple scenes. Here, we propose a collaborative interface including electrooculography (EOG) and tactile perception for fast and accurate 3D human-machine interaction. The EOG signals are mainly used for fast, convenient, and contactless 2D (XY-axis) interaction, and the tactile sensing interface is mainly utilized for complex 2D movement control and Z-axis control in the 3D interaction. The honeycomb graphene electrodes for the EOG signal acquisition and tactile sensing array are prepared by a laser-induced process. Two pairs of ultrathin and breathable honeycomb graphene electrodes are attached around the eyes for monitoring nine different eye movements. A machine learning algorithm is designed to train and classify the nine different eye movements with an average prediction accuracy of 92.6%. Furthermore, an ultrathin (90 µm), stretchable (∼1000%), and flexible tactile sensing interface assembled by a pair of 4 × 4 planar electrode arrays is attached to the arm for 2D movement control and Z-axis interaction, which can realize single-point, multipoint and sliding touch functions. Consequently, the tactile sensing interface can achieve eight directions control and even more complex movement trajectory control. Meanwhile, the flexible and ultrathin tactile sensor exhibits an ultrahigh sensitivity of 1.428 kPa-1 in the pressure range 0-300 Pa with long-term response stability and repeatability. Therefore, the collaboration between EOG and the tactile perception interface will play an important role in rapid and accurate 3D human-machine interaction.