[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

Predictors of Chronic Postsurgical Pain in Elderly Patients Undergoing Hip Arthroplasty: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Identifying patients at high risk of developing chronic postsurgical pain (CPSP) is of extreme importance in order to help launch appropriate therapeutic strategies and intensive initiation of pain management. AIM: In this study, we aimed to conduct a multi-center retrospective cohort study to establish a prognostic model and a nomogram to predict the risks of CPSP in elderly patients who underwent hip arthroplasty at 6 months postoperatively. METHODS: We collected data from 736 patients aged >65 years who had undergone hip arthroplasty from October 1, 2016 to September, 30, 2018 at multiple tertiary referral centers in Guangzhou, China. All data were randomly stratified into a training set and a testing set at a ratio of 8:2. Data were analyzed via multiple logistic regression analysis with receiver operating characteristic (ROC) curves and areas under the curve. This model was further validated by estimating calibration and discrimination. A nomogram was ultimately developed. RESULTS: A total of 736 eligible patients were enrolled, 27.20% of whom developed CPSP within 6 months postoperatively. Preoperative pain in the surgical area (OR=2.456, 95% CI:1.814-3.327, P<0.001), preoperative depression state (OR=1.256, 95% CI:1.146-1.378, P<0.001), surgical type (OR=7.138, 95% CI:3.548-14.364, P<0.001), acute postoperative numerical rating scale score (OR=5.537, 95% CI:3.607-8.499, P<0.001) and analgesic type (patient-controlled epidural analgesia: OR=0.129, 95% CI:0.055-0.299, P<0.001; patient-controlled intravenous analgesia: OR=0.033, 95% CI:0.011-0.097, P<0.001) were identified as independent significant factors associated with CPSP. A prognostic model was established and further validated. An ROC curve confirmed the predictive ability of this model with a high sensitivity value of 92.12% (95% CI:86.90-95.74) and specificity value of 91.72% (95% CI:88.77-94.11). A nomogram was developed to simplify the use of the predictive model in clinical practice. CONCLUSION: This prognostic model could be of great value in clinical practice, serving as the basis for early personalized analgesic management of elderly patients undergoing hip arthroplasty.

Recyclable conductive nanoclay for direct in situ printing flexible electronics.

Liquid-metal (LM)-based flexible and stretchable electronics have attracted widespread interest in wearable health monitoring, electronic skins, and soft robotics. However, it is challenging to directly pattern LMs on soft substrates to form desirable functional circuits due to their huge surface tension and weak wettability. Here, a recyclable, self-healing conductive nanoclay is prepared by introducing nanoclay into the LM system, which possesses low fluidity and excellent adhesion to soft substrates, and combined with the stamping process, flexible electronics can be printed directly and quickly in situ. Conductive nanoclay possesses great conductivity, significant electrical response to deformation, very low electric hysteresis and excellent damage mitigation ability, making it an ideal direct-printable ink for rapid manufacturing of flexible electronics. Owing to unique structure composition, conductive nanoclay can grow in a vacuum and maintain excellent conductivity, based on which vacuum-on switches that can be used in extreme environments such as outer space are fabricated without complex structural design. Furthermore, the electronic tattoos possessing excellent conformity with the skin were directly printed in situ on the wrist and can be employed to monitor the motion of the wrist along two different bending directions.

3D Printing of Physical Organ Models: Recent Developments and Challenges.

Physical organ models are the objects that replicate the patient-specific anatomy and have played important roles in modern medical diagnosis and disease treatment. 3D printing, as a powerful multi-function manufacturing technology, breaks the limitations of traditional methods and provides a great potential for manufacturing organ models. However, the clinical application of organ model is still in small scale, facing the challenges including high cost, poor mimicking performance and insufficient accuracy. In this review, the mainstream 3D printing technologies are introduced, and the existing manufacturing methods are divided into "directly printing" and "indirectly printing", with an emphasis on choosing suitable techniques and materials. This review also summarizes the ideas to address these challenges and focuses on three points: 1) what are the characteristics and requirements of organ models in different application scenarios, 2) how to choose the suitable 3D printing methods and materials according to different application categories, and 3) how to reduce the cost of organ models and make the process simple and convenient. Moreover, the state-of-the-art in organ models are summarized and the contribution of 3D printed organ models to various surgical procedures is highlighted. Finally, current limitations, evaluation criteria and future perspectives for this emerging area are discussed.

High-Performance Auxetic Bilayer Conductive Mesh-Based Multi-Material Integrated Stretchable Strain Sensors.

High-performance stretchable strain sensors, particularly those with high sensitivity and broad sensing range, are highly important for wearable devices. Herein, a novel auxetic bilayer conductive mesh strain sensor (ABSS), composed of multi-hardness silicones, is proposed and fabricated by the direct ink writing 3D printing and ink spraying technique. The bilayer conductive mesh comprises a thin layer of high-conductive and crack-prone single-walled carbon nanotubes (SWCNTs) coated on a stretchable carbon-black-doped Ecoflex silicone rubber (CB/Ecoflex) mesh. The former serves as the dominant sensing material by generating SWCNT cracks in the full strain range, while the latter mainly plays the roles of both generating the resistance change and maintaining the conductive paths under high strain conditions. The presence of high-hardness auxetic frame contributes to the formation of longitudinal SWCNT cracks on transverse meshes, enhancing the sensitivity of the sensors. It is shown that the synergistic effect of the bilayer conductive mesh, strain concentration, and auxetic deformation strategy endow ABSS with a high gauge factor (∼ 13.4) that is 6.6 times larger than that of the common sensor. Additionally, this study demonstrates the superior sensing performance of the ABSS for wearable applications including swallowing recognition, respiration monitoring, and joint movement detection.

A flexible porous chiral auxetic tracheal stent with ciliated epithelium.

Tracheal stent placement is a principal treatment for tracheobronchial stenosis, but complications such as mucus plugging, secondary stenosis, migration, and strong foreign body sensation remain unavoidable challenges. In this study, we designed a flexible porous chiral tracheal stent intended to reduce or overcome these complications. The stent was innovatively designed with a flexible tetrachiral and anti-tetrachiral hybrid structure as the frame and hollows filled with porous silicone sponge. Detailed finite element analysis (FEA) showed that the designed frame can maintain a Poisson's ratio that is negative or close to zero at up to 50% tensile strain. This contributes to improved airway ventilation and better resistance to migration during physiological activities such as respiration and neck movement. The preparation process combined indirect 3D printing with gas foaming and particulate leaching methods to efficiently fabricate the stent. The stent was then subjected to uniaxial tension and local radial compression tests, which indicated that it not only has the same desirable auxetic performance but also has flexibility similar to the native trachea. The porous sponge facilitated the adhesion of cells, allowed nutrient diffusion, and would prevent the ingrowth of granulation tissue. Furthermore, a ciliated tracheal epithelium similar to that of the native trachea was differentiated from normal human bronchial primary epithelial cells on the internal wall of the stent under air-liquid interface conditions. These results suggest that the designed stent has the potential for application in the treatment of tracheobronchial stenosis.

A printing-spray-transfer process for attaching biocompatible and antibacterial coatings to the surfaces of patient-specific silicone stents.

An antibacterial coating with stable antibacterial properties and favorable biocompatibility is recognized as an effective method to prevent bacterial adhesion and biofilm formation on biomedical implant surfaces. In this study, a convenient and low-cost printing-spray-transfer process was proposed that enables reliably attaching antibacterial and biocompatible coatings to patient-specific silicone implant surfaces. A desktop three-dimensional printer was used to print the mold of silicone implant molds according to the characteristics of the diseased areas. Multiwalled carbon nanotubes (MWCNTs) uniformly decorated with silver nanoparticles (AgNPs/CNTs) were synthesized as the antibacterial materials for the spray process. The well-distributed AgNPs/CNT coating was anchored to the silicone surface through an in-mold transfer printing process. Stable adhesion of the coatings was assessed via tape testing and UV-vis spectra. Hardly any AgNPs/CNTs peeled off the substrate, and the adhesion was rated at 4B. Antibacterial activity, Ag release, cell viability and morphology were further assessed, revealing high antibacterial activity and great biocompatibility. The process proposed herein has potential applications for fabricating stable antibacterial coatings on silicone implant surfaces, especially for patient-specific silicone implants such as silicone tracheal stents.

A Novel Anti-Microbial Peptide from Pseudomonas, REDLK Induced Growth Inhibition of Leishmania tarentolae Promastigote In Vitro.

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway.

BACKGROUND/AIMS: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. METHODS: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. RESULTS: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. CONCLUSION: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

Self-Sensing of Position-Related Loads in Continuous Carbon Fibers-Embedded 3D-Printed Polymer Structures Using Electrical Resistance Measurement.

Condition monitoring in polymer composites and structures based on continuous carbon fibers show overwhelming advantages over other potentially competitive sensing technologies in long-gauge measurements due to their great electromechanical behavior and excellent reinforcement property. Although carbon fibers have been developed as strain- or stress-sensing agents in composite structures through electrical resistance measurements, the electromechanical behavior under flexural loads in terms of different loading positions still lacks adequate research, which is the most common situation in practical applications. This study establishes the relationship between the fractional change in electrical resistance of carbon fibers and the external loads at different loading positions along the fibers' longitudinal direction. An approach for real-time monitoring of flexural loads at different loading positions was presented simultaneously based on this relationship. The effectiveness and feasibility of the approach were verified by experiments on carbon fiber-embedded three-dimensional (3D) printed thermoplastic polymer beam. The error in using the provided approach to monitor the external loads at different loading positions was less than 1.28%. The study fully taps the potential of continuous carbon fibers as long-gauge sensory agents and reinforcement in the 3D-printed polymer structures.

Seroprevalence of Dirofilaria immitis in Cats from Liaoning Province, Northeastern China.

The present study was performed to investigate the seroprevalence and risk factors for Dirofilaria immitis infection in cats from Liaoning province, northeastern China. From October 2014 to September 2016, sera of 651 cats, including 364 domestic cats and 287 feral cats (332 females and 319 males) were assessed. They were tested for the presence of D. immitis antigen using SNAP Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age and rearing conditions (feral or domestic) were found to be associated with the prevalence of D. immitis. The prevalence was significantly higher in feral cats compared with domestic cats (8.4% vs 1.4%, P<0.01). There was no significant difference between males and females (4.7% vs 4.2%, P>0.05), but older cats (≥3 years old) showed a statistically higher prevalence compared with younger cats (<3 years old) in feral populations (16.8 vs 2.4%, P<0.01), while the difference between the age groups was not statistically significant in domestic cats (2.4% vs 0.51%, P>0.05), all these results suggest that outdoor exposure time may be one of the most important factors for D. immitis prevalence in cats. Results reveal that D. immitis are prevalence in domestic and feral cats in northeastern China, which indicates that appropriate preventive measures should be taken to decrease the incidence of feline heartworm disease in Liaoning province, northeastern China.

Toxoplasma gondii: Protective immunity induced by a DNA vaccine expressing GRA1 and MIC3 against toxoplasmosis in BALB/c mice.

The intracellular parasite Toxoplasma gondii is a major cause of abortion and neonatal loss in livestock, and can cause severe illness to human with weakened immune system. The heavy incidence and severe consequence indicate the development of vaccines against T. gondii is required. In this study, DNA vaccines encoding GRA1 and MIC3 antigens were developed. The parasite-specific immune responses and protection efficiency against toxoplasmosis by these DNA vaccines were evaluated in BALB/c mice. The results demonstrated that the IgG antibody production was significantly increased in multi-antigenic vaccine encoding GRA1 and MIC3 immunized group, as well as the IFN-γ level, when compared with single-gene vaccines and controls groups (p < 0.05). Two weeks after the final vaccination, the mice were challenged with either 1 × 10(4) or 1 × 10(2) RH strain tachyzoites, and the mortality and parasite reduction were observed. The multi-antigenic vaccine encoding GRA1 and MIC3 lead to the longest survival time as well as the less parasite-loads in brain and liver of immunized mice (p < 0.01). The present study indicates that the GRA1 and MIC3 showed the potential as target for vaccine investigation against toxoplasmosis. And the immune efficacy induced by multi-antigenic vaccine encoding GRA1 and MIC3 was better than that induced by single-antigenic vaccines alone.

Effects of Glucose Concentration on Propofol Cardioprotection against Myocardial Ischemia Reperfusion Injury in Isolated Rat Hearts.

The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5.5 mM (LG) or 8 mM (G) in the absence or presence of propofol (5 µg/mL) or propofol plus trimetazidine (TMZ). Hearts were subjected to 35 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial infarct size (IS) and cardiac CK-MB were significantly higher in LG than in G group (P < 0.05), associated with reduced left ventricular developed pressure and increases in postischemic cardiac contracture. Cardiac 15-F2t-isoprostane was higher, accompanied with higher cardiac lipid transporter CD36 protein expression in LG. Propofol reduced IS, improved cardiac function, and reduced CD36 in G but not in LG. TMZ facilitated propofol cardioprotection in LG. Therefore, isolated heart with low glucose lost sensitivity to propofol treatment through enhancing FA oxidation and TMZ supplementation restored the sensitivity to propofol.

The structure, stability, and electronic properties of ultra-thin BC2N nanotubes: a first-principles study.

Rapid developments of the silicon electronics industry have close to the physical limits and nanotube materials are the ideal materials to replace silicon for the preparation of next generation electronic devices. Boron-carbon-nitrogen nanotubes (BCNNT) can be formed by joining carbon nanotube (CNT) and boron nitride nanotube (BNNT) segments, and BC2N nanotubes have been widely and deeply studied. Here, we employed first-principles calculations based on density function theory (DFT) to study the structure, stability, and electronic properties of ultra thin (4 Å diameter) BC2N nanotubes. Our results showed that the cross sections of BC2N nanotubes can transform from round to oval when CNT and BNNT segments are parallel to the tube axis. It results when the curvature of BNNT segments become larger than CNT segments. Further, we found the stability of BC2N nanotubes is sensitive to the number of B-N bonds, and the phase segregation of BNNT and CNT segments is energetically favored. We also obtained that all (3,3) BC2N nanotubes are semiconductor, whereas (5,0) BC2N nanotubes are conductor when CNT and BNNT segments are perpendicular to the tube axis; and semiconductor when CNT and BNNT segments are parallel to the tube axis. These electronic properties are abnormal when compared to the relative big ones.

Research on a power management system for thermoelectric generators to drive wireless sensors on a spindle unit.

Thermoelectric energy harvesting is emerging as a promising alternative energy source to drive wireless sensors in mechanical systems. Typically, the waste heat from spindle units in machine tools creates potential for thermoelectric generation. However, the problem of low and fluctuant ambient temperature differences in spindle units limits the application of thermoelectric generation to drive a wireless sensor. This study is devoted to presenting a transformer-based power management system and its associated control strategy to make the wireless sensor work stably at different speeds of the spindle. The charging/discharging time of capacitors is optimized through this energy-harvesting strategy. A rotating spindle platform is set up to test the performance of the power management system at different speeds. The experimental results show that a longer sampling cycle time will increase the stability of the wireless sensor. The experiments also prove that utilizing the optimal time can make the power management system work more effectively compared with other systems using the same sample cycle.

Establishment and application of a loop-mediated isothermal amplification method for simple, specific, sensitive and rapid detection of Toxoplasma gondii.

The Loop-mediated isothermal amplification (LAMP) method amplifies DNA with high simply, specificity, sensitivity and rapidity. In this study, A LAMP assay with 6 primers targeting a highly conserved region of the GRA1 gene was developed to diagnose Toxoplasma gondii. The reaction time of the LAMP assay was shortened to 30 min after optimizing the reaction system. The LAMP assay was found to be highly specific and stable. The detection limit of the LAMP assay was 10 copies, the same as that of the conventional PCR. We used the LAMP assay to develop a real-time fluorogenic protocol to quantitate T. gondii DNA and generated a log-linear regression plot by plotting the time-to-threshold values against genomic equivalent copies. Furthermore, the LAMP assay was applied to detect T. gondii DNA in 423 blood samples and 380 lymph node samples from 10 pig farms, and positive results were obtained for 7.8% and 8.2% of samples, respectively. The results showed that the LAMP method is slightly more sensitive than conventional PCR (6.1% and 7.6%). Positive samples obtained from 6 pig farms. The LAMP assay established in this study resulted in simple, specific, sensitive and rapid detection of T. gondii DNA and is expected to play an important role in clinical detection of T. gondii.

[Biological and phylogenetic analysis of first isolate of Tahyna virus in China].

In 2006, the first Chinese Tahyna virus isolate (XJ0625) was obtained in Xinjiang province and human infection were found in the same region. In this study, cell culture, animal experiments, electron microscopy, immunofluorescence assay and cross neutralization tests were performed to see the cell susceptibility, animal pathogenicity, morphology and antigenic and other biological characteristics of XJ0625. In addition, molecular biology software was used to analyze the characteristics of molecular evolution. The results showed that BHK-21 cell line was susceptible to XJ0625 and the virus was lethal to suckling mice when injected by intracranial ways. Similar to the other Bunyavirus, Tahyna virus is spherical enveloped virus under electron microscopy. XJ0625 infected cells showed strong fluorescent signal and could be neutralized by immune asities fluid with immnity to protype Tahyna virus Bardos 92. The sequence of the S and M segments showed 91.8% and 81.9% homology with Bardos 92.

[Effects of intrathecal escin and clonidine in the treatment of neuropathic pain in rats].

OBJECTIVE: To investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism. METHODS: Ninety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs. RESULTS: MPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (P<0.05). Intrathecal escin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (P<0.01) and attenuated the action of the combination treatment with escin and clonidine (P<0.05). CONCLUSION: Intrathecal escin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.