Highly homologous miR-135a and miR-135b converting non-small cell lung cancer from suppression to progression via enhancer switching.

microRNAs (miRNAs) are short non-coding RNAs that have been increasingly recognized for their significant roles in the progression of cancer. Distinct miRNAs exhibit diverse functions attributed to variations in their sequences. As a result of possessing highly homologous seed sequences, these miRNAs target overlapping or similar gene sets, thus performing analogous roles. However, different from this sight, our study discovered that miR-135a-5p and miR-135b-5p, despite differing by only one nucleotide, exhibit distinct functional roles. Using non-small cell lung cancer (NSCLC) as a paradigm, our findings unveiled the downregulation of miR-135a-5p and upregulation of miR-135b-5p within NSCLC through TCGA database. Consequently, we further investigated their functional differences in A549 cells. Overexpression of miR-135b-5p enhanced the proliferation and migration capabilities of A549 cells, whereas miR-135a-5p transfection exhibited the opposite effect. We demonstrated that the activation of specific enhancers serves as a crucial mechanism underlying the disparate functions exerted by miR-135a-5p and miR-135b-5p in the context of NSCLC, consequently instigating a shift from inhibition to activation in NSCLC progression. Finally, we validated through animal experiments that miR-135b-5p promoted tumor progression, while miR-135a-5p exerted inhibitory effects on NSCLC development. This study offers a novel perspective for researchers to elucidate functional disparities exhibited by highly homologous miRNAs (miR-135a-5p and miR-135b-5p) in the context of NSCLC, along with the transition from inhibitory to progressive states in NSCLC. This study provides a solid foundation for future investigations into the functional roles of highly homologous miRNAs in pathological situation.

[Design and Fabrication of Porous Implants Manufactured by 3D Printing].

Different porous structures were studied through finite element analysis and then optimal porous structure was selected for the orthopedic applications. The optimal Voronoi structure was designed and fabricated using 3D printing. The mechanical properties and osseointegration ability were both investigated. The mechanical tests showed that the tensile strength, compressive strength and bending strength of Voronoi structures were obviously higher than that of the human bone, and the modulus of Voronoi structures were similar to human bone. In addition, the animal experimental results exhibited that obvious bone ingrowth was found from Month 1 to Month 6. This study provides some theoretical references for the orthopedic application of porous structures.

[Research on Locating Device for the Entry Point of Intramedullary Nail Based on Inertial Navigation].

Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.

Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network.

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.

Effect of Internal Mechanical Environment of Porous Scaffolds on Mechano-driven Bone Ingrowth: A Numerical Study.

Porous cages with lower global stiffness induce more bone ingrowth and enhance bone-implant anchorage. However, it's dangerous for spinal fusion cages, which usually act as stabilizers, to sacrifice global stiffness for bone ingrowth. Intentional design on internal mechanical environment might be a promising approach to promote osseointegration without undermining global stiffness excessively. In this study, three porous cages with different architectures were designed to provide distinct internal mechanical environments for bone remodeling during spinal fusion process. A design space optimization-topology optimization based algorithm was utilized to numerically reproduce the mechano-driven bone ingrowth process under three daily load cases, and the fusion outcomes were analyzed in terms of bone morphological parameters and bone-cage stability. Simulation results show that the uniform cage with higher compliance induces deeper bone ingrowth than the optimized graded cage. Whereas, the optimized graded cage with the lowest compliance exhibits the lowest stress at the bone-cage interface and better mechanical stability. Combining the advantages of both, the strain-enhanced cage with locally weakened struts offers extra mechanical stimulus while keeping relatively low compliance, leading to more bone formation and the best mechanical stability. Thus, the internal mechanical environment can be well-designed via tailoring architectures to promote bone ingrowth and achieve a long-term bone-scaffold stability.

Morphological and Physiological Mechanisms of Melatonin on Delaying Drought-Induced Leaf Senescence in Cotton.

Leaf senescence reduces the photosynthetic capacity of leaves, thus significantly affecting the growth, development, and yield formation of cotton. Melatonin (MT) is a multipotent substance proven to delay leaf senescence. However, its potential mechanism in delaying leaf senescence induced by abiotic stress remains unclear. This study aimed to explore the effect of MT on delaying drought-induced leaf senescence in cotton seedlings and to clarify its morphological and physiological mechanisms. Drought stress upregulated the leaf senescence marker genes, destroyed the photosystem, and led to excessive accumulation of reactive oxygen species (ROS, e.g., H2O2 and O2-), thus accelerating leaf senescence. However, leaf senescence was significantly delayed when 100 µM MT was sprayed on the leaves of the cotton seedlings. The delay was embodied by the increased chlorophyll content, photosynthetic capacity, and antioxidant enzyme activities, as well as decreased H2O2, O2-, and abscisic acid (ABA) contents by 34.44%, 37.68%, and 29.32%, respectively. MT significantly down-regulated chlorophyll degradation-related genes and senescence marker genes (GhNAC12 and GhWRKY27/71). In addition, MT reduced the chloroplast damage caused by drought-induced leaf senescence and maintained the integrity of the chloroplast lamellae structure under drought stress. The findings of this study collectively suggest that MT can effectively enhance the antioxidant enzyme system, improve photosynthetic efficiency, reduce chlorophyll degradation and ROS accumulation, and inhibit ABA synthesis, thereby delaying drought-induced leaf senescence in cotton.

Reproducible protocol to obtain and measure first-order relay human thalamic white-matter tracts.

The "primary" or "first-order relay" nuclei of the thalamus feed the cerebral cortex with information about ongoing activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thalamocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nucleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffusion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.

[Research Progress of Physiologic Parameters Monitoring Technology for Critical Neonates].

Physiological parameter monitoring is essential to medical staff to evaluate, diagnose and treat patients in neonatal intensive care unit (NICU). Monitoring in NICU includes basic vital signal monitoring and functional monitoring. Basic vital signal monitoring (including ECG, respiration, SpO2, blood pressure, temperature) is advanced and focus on study of usability, continuity and anti-interference. Functional monitoring (including respiratory function, circulatory function, cerebral function) still focus on study of monitoring precision and reliability. Meanwhile, video monitoring and artifact intelligence have presented well performance on improving monitoring precision and anti-interference. In this article, the main parameters and relevant measurement technology for monitoring critical neonates were described.

[Clinical Significance of Application of Comprehensive Management of Atrial Fibrillation].

OBJECTIVE: To improve the accuracy of detection of arrhythmia in patients with atrial fibrillation (AF) and to enable the scientific management and assessment of AF, a comprehensive management tool for AF is proposed, which is helpful for medical staff to systematically evaluate and manage patients with AF. METHODS: A professional view of atrial fibrillation (AF View) was designed to unify the statistical information of AF event, and display the statistical distribution data of AF events and trend data of other physiological parameters or characteristics such as heart rate, blood pressure and ST value during the patient monitoring period in a centralized manner. A multi-dimensional summary information was obtained from AF View. In addition, the monitoring period and monitoring parameters or characteristics in the AF View can be adjusted so as to obtain the summary information under different periods and parameters or characteristics, and get the condition of AF of the patient. RESULTS: Accurate detection and comprehensive management of AF were achieved. CONCLUSIONS: The application of AF comprehensive management proposed in this study is helpful for medical staff to know the condition of AF patients in real time and adjust the treatment plan in time.

High-Contrast Fluorescence Diagnosis of Cancer Cells/Tissues Based on ß-Lapachone-Triggered ROS Amplification Specific in Cancer Cells.

Discrimination of cancer cells/tissues from normal ones is of critical importance for early diagnosis and treatment of cancers. Herein, we present a new strategy for high-contrast fluorescence diagnosis of cancer cells/tissues based on ß-Lapachone (ß-Lap, an anticancer agent) triggered ROS (reactive oxygen species) amplification specific in cancer cells/tissues. With the strategy, a wide range of cancer cells/tissues, including surgical tissue specimens harvested from patients, were distinguished from normal ones by using a combination of ß-Lap and a Si-rhodamine-based NIR fluorescent ROS probe PSiR3 developed in this work with average tumor-to-normal (T/N) ratios up to 15 in cell level and 24 in tissue level, far exceeding the clinically acceptable threshold of 2.0. What's more, the strategy allowed the fluorescence discrimination of tumor tissues from inflammatory ones based on whether a marked fluorescence enhancement could be induced when treated with PSiR3 and ß-Lap/PSiR3 combination, respectively.

[Research on Patient Monitoring Alarms in ICU and NICU].

OBJECTIVE: The patient monitors were used to explore the alarm actuality in a ICU and NICU to investigate the awareness and reaction of medical staff to alarms. METHODS: A series of surveys and interviews were taken to acquire clinicians' feelings and attitudes to monitoring alarms. The researchers were scheduled to track the alarms with annotations, and collect the alarm data of patient monitors using central monitoring system. RESULTS: A total of 235 387 and 67 783 alarms occurred in ICU and NICU respectively. The average alarm rate was about 142 alarms/patient-day in ICU and 96 alarms/patient-day in NICU. CONCLUSIONS: There remains alarm fatigue in ICU and NICU, the main reason is the large number of false alarms and clinically irrelevant alarms. In addition, patient monitor is still in the level of threshold alarms or combined alarms, the data integrity and intelligence level need to be improved in future.

[A Survey of Patient Monitoring Alarms in Cardiac Care Units].

OBJECTIVE: The patient monitors were used to explore the alarm fatigue in a cardiac care unit and to investigate the awareness and reaction of nurse to alarms. METHODS: A semi-structured survey was taken to acquire nurses' feeling and knowledge about monitoring alarm. Three full-time researchers were scheduled to track the alarms with annotations, and analyze the alarm data of 12 patient monitors using central monitoring system. RESULTS: A total of 72 310 unique alarms occurred in the 67-day study period. About 75.7% of them were physiological alarms and less than 10% of medium-low alarms were false positives. The average alarm rate was 128 alarms/patient-day. CONCLUSIONS: There remains alarm fatigue in CCU, the alarm accuracy has improved than the past by applying new technologies. In some cases, clinicians will pay more attention to trend alarm and combination alarm.

[Review of Physiological Parameters Monitoring Technology in the ICU].

Physiological parameters monitoring is essential to direct medical staff to evaluate, diagnose and treat critical patients quantitatively. ECG, blood pressure, SpO2, respiratory rate and body temperature are the basic vital signs of patients in the ICU. The measuring methods are relatively mature at present, and the trend is to be wireless and more accurate and comfortable. Hemodynamics, oxygen metabolism and microcirculation should be taken seriously during the treatment of acute critical patients. The related monitoring technology has made significant progress in recent years, the trend is to reduce the trauma and improve the accuracy and usability. With the development of machine vision and data fusion technology, the identification of patient behavior and deterioration has become hot topics. This review is focused on current parameters monitoring technologies, aims to provide reference for future related research.

Carbon-Dipyrromethenes: Bright Cationic Fluorescent Dyes and Potential Application in Revealing Cellular Trafficking of Mitochondrial Glutathione Conjugates.

Boron-dipyrromethenes (Bodipys), since first reported in 1968, have emerged as a fascinating class of dyes in the past few decades due to their excellent photophysical properties including bright fluorescence, narrow emission bandwidth, resistance to photobleaching, and environment insensitivity. However, typical Bodipys are highly lipophilic, which often results in nonfluorescent aggregates in aqueous solution and also severely limits their bioavailability to cells and tissues. In this work, based on a simple one-atom B → C replacement in the Bodipy scaffold, we present a new class of carbon-dipyrromethenes (Cardipys for short) fluorescent dyes with tunable emission wavelengths covering the visible and near-infrared regions. These Cardipys not only retain the excellent photophysical properties of conventional Bodipys but also show improved water solubility and photostability due to their cationic character. Moreover, the cationic character also makes them extremely easy to penetrate the cell membrane and specifically accumulate into mitochondria without resorting to any mitochondria-targeted groups. Interestingly, several Cardipys bearing active styryl groups could serve as fluorescent indicators to map cellular trafficking of the glutathione conjugates produced within mitochondria under the catalysis of glutathione S-transferase (GST), thus showing potential in either exploring the detoxification mechanism of the mitochondrial GST/GSH system or evaluating the drug resistance of cancer cells that is closely related with GST activity.

[Research of Methods to Reduce Alarm Fatigue of Monitoring System].

OBJECTIVE: In order to solve alarm fatigue, the algorithm optimization strategies were researched to reduce false and worthless alarms. METHODS: A four-lead arrhythmia analysis algorithm, a multiparameter fusion analysis algorithm, an intelligent threshold reminder, a refractory period delay technique were proposed and tested with collected 28 679 alarms in multi-center study. RESULTS: The sampling survey indicate that the 80.8% of arrhythmia false alarms were reduced by the four-lead analysis, the 55.9% of arrhythmia and pulse false alarms were reduced by the multi-parameter fusion analysis, the 28.0% and 29.8% of clinical worthless alarms were reduced by the intelligent threshold and refractory period delay techniques respectively. Finally, the total quantity of alarms decreased to 12 724. CONCLUSIONS: To increase the dimensionality of parametric analysis and control the alarm limits and delay time are conducive to reduce alarm fatigue in intensive care units.

[A Mattress System of Recognizing Sleep Postures Based on BCG Signal].

Sleep posture recognition is the core index of diagnosis and treatment of positional sleep apnea syndrome. In order to detect body postures noninvasively, we developed a portable approach for sleep posture recognition using BCG signals with their morphological difference. A type of piezo-electric polymer film sensor was applied to the mattress to acquire BCG, the discrete wavelet transform with cubic B-spline was used to extract characteristic parameters and a naive Bayes learning phase was adapted to predict body postures. Eleven healthy subjects participated in the sleep simulation experiments. The results indicate that the mean error obtained from heart rates was 0.04±1.3 beats/min (±1.96 SD). The final recognition accuracy of four basic sleep postures exceeded 97%, and the average value was 97.9%. This measuring system is comfortable and accurate, which can be streamlined for daily sleep monitoring application.

[Wearable Medical Devices' MCU Selection Analysis Based on the ARM Cortex-MO+ Architecture].

According to the characteristics of low cost, high performance, high integration and long battery life of wearable medical devices, the mainstream low-power microcontroller(MCU) series were compared, and came to the conclusion that the MCU series based on ARM Cortex-M0+ architecture were suitable for the development of wearable medical devices. In aspects of power consumption, operational performance, integrated peripherals and cost, the MCU series based on Cortex-M0+ architecture of primary semiconductor companies were compared, aimed at providing the guides of MCU selection for wearable medical devices.

[MCU selection analysis in portable electronic medical instrument design].

Around the features of low power and high integration of portable electronic medical equipment design, the primary low power MCU series from the current semiconductor manufacturers were compared. The analysis results showed that the 32-bit MCUs based on the low cost and high energy efficient ARM Cortex-M architectures, have comprehensive advantages on power level, operational performance and integrated peripherals obviously.

[Optimal design of portable ambulatory blood pressure monitor based on STM32L].

Based on the 32-bit ultra low power microcontroller STM32L151RBT6 using ARM Cortex-M3 kernel, the portable ambulatory blood pressure monitor powered by two AA batteries was designed. In order to insure the stability of power supply and prevent overpressure of cuff, super capacitor technology and new kind of safety logic circuits were used. The experimental result shows that: this solution is accurate and stable, which has high safety coefficient and a great clinical application value.

Mechano-driven intervertebral bone bridging via oriented mechanical stimulus in a twist metamaterial cage: An in silico study.

Stiffer cages provide sufficient mechanical support but fail to promote bone ingrowth due to stress shielding. It remains challenging for fusion cage to satisfy both bone bridging and mechanical stability. Here we designed a fusion cage based on twist metamaterial for improved bone ingrowth, and proved its superiority to the conventional diagonal-based cage in silico. The fusion process was numerically reproduced via an injury-induced osteogenesis model and the mechano-driven bone remodeling algorithm, and the outcomes fusion effects were evaluated by the morphological features of the newly-formed bone and the biomechanical behaviors of the bone-cage composite. The twist-based cages exhibited oriented bone formation in the depth direction, in comparison to the diagonal-based cages. The axial stiffness of the bone-cage composites with twist-based cages was notably higher than that with diagonal-based cages; meanwhile, the ranges of motion of the twist-based fusion segment were lower. It was concluded that the twist metamaterial cages led to oriented bone ingrowth, superior mechanical stability of the bone-cage composite, and less detrimental impacts on the adjacent bones. More generally, metamaterials with a tunable displacement mode of struts might provide more design freedom in implant designs to offer customized mechanical stimulus for osseointegration.