Exploring optimal settings for safe and effective thulium fibre laser lithotripsy in a kidney model.

OBJECTIVES: To explore the optimal laser settings and treatment strategies for thulium fibre laser (TFL) lithotripsy, namely, those with the highest treatment efficiency, lowest thermal injury risk, and shortest procedure time. MATERIALS AND METHODS: An in vitro kidney model was used to assess the efficacy of TFL lithotripsy in the upper calyx. Stone ablation experiments were performed on BegoStone phantoms at different combinations of pulse energy (EP ) and frequency (F) to determine the optimal settings. Temperature changes and thermal injury risks were monitored using embedded thermocouples. Experiments were also performed on calcium oxalate monohydrate (COM) stones to validate the optimal settings. RESULTS: High EP /low F settings demonstrated superior treatment efficiency compared to low EP /high F settings using the same power. Specifically, 0.8 J/12 Hz was the optimal setting, resulting in a twofold increase in treatment efficiency, a 39% reduction in energy expenditure per unit of ablated stone mass, a 35% reduction in residual fragments, and a 36% reduction in total procedure time compared to the 0.2 J/50 Hz setting for COM stones. Thermal injury risk assessment indicated that 10 W power settings with high EP /low F combinations remained below the threshold for tissue injury, while higher power settings (>10 W) consistently exceeded the safety threshold. CONCLUSIONS: Our findings suggest that high EP /low F settings, such as 0.8 J/12 Hz, are optimal for TFL lithotripsy in the treatment of COM stones. These settings demonstrated significantly improved treatment efficiency with reduced residual fragments compared to conventional settings while keeping the thermal dose below the injury threshold. This study highlights the importance of using the high EP /low F combination with low power settings, which maximizes treatment efficiency and minimizes potential thermal injury. Further studies are warranted to determine the optimal settings for TFL for treating kidney stones with different compositions.

Advances in methane emissions from agricultural sources: Part I. Accounting and mitigation.

Methane is one of the major greenhouse gases (GHGs) and agriculture is recognized as its primary emitter. Methane accounting is a prerequisite for developing effective agriculture mitigation strategies. In this review, methane accounting methods and research status for various agricultural emission source including rice fields, animal enteric fermentation and livestock and poultry manure management were overview, and the influencing factors of each emission source were analyzed and discussed. At the same time, it analyzes the different research efforts involving agricultural methane accounting and makes recommendations based on the actual situation. Finally, mitigation strategies based on accounting results and actual situation are proposed. This review aims to provide basic data and reference for agriculture-oriented countries and regions to actively participate in climate action and carry out effective methane emission mitigation.

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

Increased risk of olfactory and taste dysfunction in the United States psoriasis population.

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.

Model-based simulations of pulsed laser ablation using an embedded finite element method.

A model of thermal ablation with application to multi-pulsed laser lithotripsy is presented. The approach is based on a one-sided Stefan-Signorini model for thermal ablation, and relies on a level-set function to represent the moving interface between the solid phase and a fictitious gas phase (representing the ablated material). The model is discretized with an embedded finite element method, wherein the interface geometry can be arbitrarily located relative to the background mesh. Nitsche's method is adopted to impose the Signorini condition on the moving interface. A bound constraint is also imposed to deal with thermal shocks that can arise during representative simulations of pulsed ablation with high-power lasers. We report simulation results based on experiments for pulsed laser ablation of wet BegoStone samples treated in air, where Begostone has been used as a phantom material for kidney stone. The model is calibrated against experimental measurements by adjusting the percentage of incoming laser energy absorbed at the surface of the stone sample. Simulation results are then validated against experimental observations for the crater area, volume, and geometry as a function of laser pulse energy and duration. Our studies illustrate how the spreading of the laser beam from the laser fiber tip with concomitantly reduced incident laser irradiance on the damaged crater surface explains trends in both the experimental observations and the model-based simulation results.

Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow.

One of the earliest events in cellular mechanotransduction is often an increase in intracellular calcium concentration associated with intracellular calcium waves (ICWs) in various physiologic or pathophysiologic processes. Although cavitation-induced calcium responses are believed to be important for modulating downstream bioeffects such as cell injury and mechanotransduction in ultrasound therapy, the fundamental mechanisms of these responses have not been elucidated. In this study, we investigated mechanistically the ICWs elicited in single HeLa cells by the tandem bubble-induced jetting flow in a microfluidic system. We identified two distinct (fast and slow) types of ICWs at varying degrees of flow shear stress-induced membrane deformation, as determined by different bubble standoff distances. We showed that ICWs were initiated by an extracellular calcium influx across the cell membrane nearest to the jetting flow, either primarily through poration sites for fast ICWs or opening of mechanosensitive ion channels for slow ICWs, which then propagated in the cytosol via a reaction-diffusion process from the endoplasmic reticulum. The speed of ICW (CICW ) was found to correlate strongly with the severity of cell injury, with CICW in the range of 33 µm/s to 93 µm/s for fast ICWs and 1.4 µm/s to 12 µm/s for slow ICWs. Finally, we demonstrated that micrometer-sized beads attached to the cell membrane integrin could trigger ICWs under mild cavitation conditions without collateral injury. The relation between the characteristics of ICW and cell injury, and potential strategies to mitigate cavitation-induced injury while evoking an intracellular calcium response, may be particularly useful for exploiting ultrasound-stimulated mechanotransduction applications in the future.

Tri-modality cavitation mapping in shock wave lithotripsy.

Shock wave lithotripsy (SWL) has been widely used for non-invasive treatment of kidney stones. Cavitation plays an important role in stone fragmentation, yet it may also contribute to renal injury during SWL. It is therefore crucial to determine the spatiotemporal distributions of cavitation activities to maximize stone fragmentation while minimizing tissue injury. Traditional cavitation detection methods include high-speed optical imaging, active cavitation mapping (ACM), and passive cavitation mapping (PCM). While each of the three methods provides unique information about the dynamics of the bubbles, PCM has most practical applications in biological tissues. To image the dynamics of cavitation bubble collapse, we previously developed a sliding-window PCM (SW-PCM) method to identify each bubble collapse with high temporal and spatial resolution. In this work, to further validate and optimize the SW-PCM method, we have developed tri-modality cavitation imaging that includes three-dimensional high-speed optical imaging, ACM, and PCM seamlessly integrated in a single system. Using the tri-modality system, we imaged and analyzed laser-induced single cavitation bubbles in both free field and constricted space and shock wave-induced cavitation clusters. Collectively, our results have demonstrated the high reliability and spatial-temporal accuracy of the SW-PCM approach, which paves the way for the future in vivo applications on large animals and humans in SWL.

Variations of stress field and stone fracture produced at different lateral locations in a shockwave lithotripter field.

During clinical procedures, the lithotripter shock wave (LSW) that is incident on the stone and resultant stress field is often asymmetric due to the respiratory motion of the patient. The variations of the LSW-stone interaction and associated fracture pattern were investigated by photoelastic imaging, phantom experiments, and three-dimensional fluid-solid interaction modeling at different lateral locations in a lithotripter field. In contrast to a T-shaped fracture pattern often observed in the posterior region of the disk-shaped stone under symmetric loading, the fracture pattern gradually transitioned to a tilted L-shape under asymmetric loading conditions. Moreover, the model simulations revealed the generation of surface acoustic waves (SAWs), i.e., a leaky Rayleigh wave on the anterior boundary and Scholte wave on the posterior boundary of the stone. The propagation of SAWs on the stone boundary is accompanied by a progressive transition of the LSW reflection pattern from regular to von Neumann and to weak von Neumann reflection near the glancing incidence and, concomitantly, the development and growth of a Mach stem, swirling around the stone boundary. The maximum tensile stress and stress integral were produced by SAWs on the stone boundary under asymmetric loading conditions, which drove the initiation and extension of surface cracks into the bulk of the stone that is confirmed by micro-computed tomography analysis.

[Impact of the Timing of Traditional Chinese Medicine Therapy on the Therapeutic Effect and Prognosis of Severe Coronavirus Disease 2019].

Objective To explore the optimal therapy time for the treatment of severe coronavirus disease 2019(COVID-19)by traditional Chinese medicine(TCM)and its influence on the therapeutic effect and prognosis. Methods The clinical data,laboratory findings,and outcomes of 64 patients with severe COVID-19 treated with TCM and western medicine in Chongqing from January 20,2020, to March 11,2020 were retrospectively analyzed.Patients were divided into early intervention group[TCM was initiated within 3 days (including day 3) after the first diagnosis of severe type/critical type COVID-19]and late intervention group[TCM was initiated after 7 days (including day 7) after the first diagnosis of severe type /critical type COVID-19].The changes in clinical parameters during the course of disease were compared between the two groups. Results On day 14,the oxygenation index was 292.5(252.0,351.0)mmHg in the early intervention group,which was significantly higher than that in the late intervention group [246.0(170.0,292.5)mmHg](P=0.005).The length of hospital stay [(18.56±1.11)d vs.(24.87±1.64)d,P=0.001],duration of ICU stay [(14.12±0.91)d vs.(20.00±1.53)d,P=0.000] and time to negativity [(16.77±1.04)d vs.(22.48±1.66)d,P=0.001] in the early intervention group were significantly shorter than those in the late intervention group.The intubation rate(7.3%)in the early intervention group was significantly lower than that in the late intervention group(30.4%)(P=0.028). Conclusion Early TCM therapy within three days after a diagnosis of severe COVID-19 can shorten the length of hospital stay,duration of ICU stay,and time to negativity and decrease intubation rate.

Activation of Piezo1 mechanosensitive ion channel in HEK293T cells by 30 MHz vertically deployed surface acoustic waves.

Ultrasound (US) has emerged as a promising noninvasive modality for neuromodulation. Despite previous evidence that US may mediate cellular response by activating mechanosensitive ion channels embedded in the cell membrane, the underlying mechanism is not well understood. In this work, we developed a vertically deployed surface acoustic wave (VD-SAW) platform that generates 30 MHz focused ultrasound wave for mechanical stimulation of single cells. We investigated the role of Piezo1 in mediating the intracellular calcium response ( [Formula: see text] ) of HEK293T cells in response to pulsed US operated at a peak pressure of 1.6 MPa with 20% duty cycle, and a total treatment time of 60 s. We observed that the elicited calcium response depends critically on the pulse repetition frequency (PRF) or burst duration of the US, as well as the presence of the Piezo1. Significantly higher [Formula: see text] increase was produced in the Piezo1-transfected (P1TF) than in the Piezo1-knockout (P1KO) HEK293T cells. Furthermore, higher calcium response probability, stronger and faster [Formula: see text] increase, and greater cell displacement were produced at 2 Hz PRF with 100 ms burst duration than 200 Hz PRF with 1 ms burst duration. Altogether, we have demonstrated that the VD-SAW platform provides a unique and versatile tool for investigating US-induced mechanotransduction at the single cell level.

Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice.

Germline stem cells are essential in the generation of both male and female gametes. In mammals, the male testis produces sperm throughout the entire lifetime, facilitated by testicular germline stem cells. Oocyte renewal ceases in postnatal or adult life in mammalian females, suggesting that germline stem cells are absent from the mammalian ovary. However, studies in mice, rats, and humans have recently provided evidence for ovarian female germline stem cells (FGSCs). A better understanding of the role of FGSCs in ovaries could help improve fertility treatments. Here, we developed a rapid and efficient method for isolating FGSCs from ovaries of neonatal mice. Notably, our FGSC isolation method could efficiently isolate on average 15 cell "strings" per ovary from mice at 1-3 days postpartum. FGSCs isolated from neonatal mice displayed the string-forming cell configuration at mitosis (i.e. a "stringing" FGSC (sFGSC) phenotype) and a disperse phenotype in postnatal mice. We also found that sFGSCs undergo vigorous mitosis especially at 1-3 days postpartum. After cell division, the sFGSC membranes tended to be connected to form sFGSCs. Moreover, F-actin filaments exhibited a cell-cortex distribution in sFGSCs, and E-cadherin converged in cell-cell connection regions, resulting in the string-forming morphology. Our new method provides a platform for isolating FGSCs from the neonatal ovary, and our findings indicate that FGCSs exhibit string-forming features in neonatal mice. The sFGSCs represent a valuable resource for analysis of ovary function and an in vitro model for future clinical use to address ovarian dysfunction.

Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.

Cavitation with bubble-bubble interaction is a fundamental feature in therapeutic ultrasound. However, the causal relationships between bubble dynamics, associated flow motion, cell deformation, and resultant bioeffects are not well elucidated. Here, we report an experimental system for tandem bubble (TB; maximum diameter = 50 ± 2 µm) generation, jet formation, and subsequent interaction with single HeLa cells patterned on fibronectin-coated islands (32 × 32 µm) in a microfluidic chip. We have demonstrated that pinpoint membrane poration can be produced at the leading edge of the HeLa cell in standoff distance Sd ≤ 30 µm, driven by the transient shear stress associated with TB-induced jetting flow. The cell membrane deformation associated with a maximum strain rate on the order of 10(4) s(-1) was heterogeneous. The maximum area strain ([Formula: see text]) decreased exponentially with Sd (also influenced by adhesion pattern), a feature that allows us to create distinctly different treatment outcome (i.e., necrosis, repairable poration, or nonporation) in individual cells. More importantly, our results suggest that membrane poration and cell survival are better correlated with area strain integral ([Formula: see text]) instead of [Formula: see text], which is characteristic of the response of materials under high strain-rate loadings. For 50% cell survival the corresponding area strain integral was found to vary in the range of 56 ∼ 123 µs with [Formula: see text] in the range of 57 ∼ 87%. Finally, significant variations in individual cell's response were observed at the same Sd, indicating the potential for using this method to probe mechanotransduction at the single cell level.

Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter.

The efficiency of shock wave lithotripsy (SWL), a noninvasive first-line therapy for millions of nephrolithiasis patients, has not improved substantially in the past two decades, especially in regard to stone clearance. Here, we report a new acoustic lens design for a contemporary electromagnetic (EM) shock wave lithotripter, based on recently acquired knowledge of the key lithotripter field characteristics that correlate with efficient and safe SWL. The new lens design addresses concomitantly three fundamental drawbacks in EM lithotripters, namely, narrow focal width, nonidealized pulse profile, and significant misalignment in acoustic focus and cavitation activities with the target stone at high output settings. Key design features and performance of the new lens were evaluated using model calculations and experimental measurements against the original lens under comparable acoustic pulse energy (E+) of 40 mJ. The -6-dB focal width of the new lens was enhanced from 7.4 to 11 mm at this energy level, and peak pressure (41 MPa) and maximum cavitation activity were both realigned to be within 5 mm of the lithotripter focus. Stone comminution produced by the new lens was either statistically improved or similar to that of the original lens under various in vitro test conditions and was significantly improved in vivo in a swine model (89% vs. 54%, P = 0.01), and tissue injury was minimal using a clinical treatment protocol. The general principle and associated techniques described in this work can be applied to design improvement of all EM lithotripters.

[Characterizing Dissolved Organic Matter (DOM) in Wastewater from Scale Pig Farms Using Three-Dimensional Excitation-Emission Matrices (3DEEM].

The properties of material composition in swine wastewater are closely related to its potential environmental effects, and it could provide theoretical bases for formulating scientific resource management measures to study the composition of organic matter in wastewater. In the present study, swine wastewater was directly collected from waste-retention basins in various scale pig farms with a different farming scale (based on the annual pig slaughter), namely Cheng Lin (CL, 5 000), Wu Yang-gao (WYG, 2 000), Wan Gu (WG, 20 000), and Zhang Bang (ZB, 24 000), located in Yujiang County of Jiangxi Province. The main purpose of this study was to characterize dissolved organic matter (DOM) in swine wastewater using three-dimensional excitation-emission matrices (3DEEM) and parallel factor analysis (PARAFAC). Results of all samples examined showed, with respect to CL and WYG farm, chemical oxygen demand (COD), total nitrogen (TN), ammonium nitrogen (NH+4), and dissolved organic carbon (DOC) concentration in swine wastewater was significantly higher than WG and ZB farm. Three DOM components, including two protein-like components (C1, C2) and one humic-like component (C3), were identified in wastewater using 3DEEM and PARAFAC. Results of linear regression showed, the fluorescence intensity of C1 linked significantly with C2 (p<0.001) and C3 (p<0.001), respectively, suggesting a same source or similar variation trend existed possibly between different DOM components. Furthermore, consistent with the variation trend of nutrient concentration in wastewater, fluorescence intensity of each DOM component in CL and WYG farm was significantly higher than WG and ZB farm. The total contribution of C1 and C2 to DOM in swine wastewater was CL (89.7%), WG (77.5%), WYG (87.9%), and ZB (72.9%), respectively, and the percentage of C3 was CL (10.3%), WG (22.5%), WYG (12.1%), and ZB (27.1%), respectively. Thus, the percentage of two protein-like components was significantly higher than humic-like in swine wastewater. Meanwhile, the fluorescence indices FI370 and humification index (HIX) of WG and ZB farm were higher than CL and WYG. In addition, Pearson correlation analysis showed that the effects of environmental parameters on fluorescence indices were different, and COD and DOC concentrations were significantly correlated with the fluorescence intensities of DOM components in swine wastewater. In summary, to a certain degree, the nutrient levels affected formation of fluorescence characteristics and DOM compositions in swine wastewater between different scale pig farms.

[Structural Analysis of Organic Matter Composition in Piggery Wastewater during the Process of Organic Degradation Based on FTIR Spectroscopy].

More and more attentions were paid on the environmental pollutions of wastewater discharged from scale pig farms, and it could provide scientific bases for formulating reasonable pollution control measures to study the structural changes of organic matter composition in piggery wastewater. In the present study, a laboratory-scale incubation experiment was carried out with piggery wastewater collected from different scale pig farms, and a continuous sampling was conducted at a certain interval during the process of incubation experiment. The main purpose of this study was to elucidate the change of structural composition of dissolved organic matter (DOM) in piggery wastewater during the process of organic degradation. All dried and solid DOM samples were achieved using filtration and freeze-drying methods. Spectral analysis of all DOM samples was completed with the application of Fourier transform infrared (FTIR) spectrometer. Results of spectral analysis showed a similar DOM structural composition was observed in the wastewater derived from different scale pig farms, and was mainly comprised of lipids, proteins, fulvic acids, polysaccharides, and phenolic compounds. With the increase in the incubation days, the percent of functional groups, related to proteins, phenolic acids, and lipids, decreased gradually and kept stable eventually, while these functional groups, linked with fulvic acids and polysaccharides, showed a significant increase and leveled off at the end. Compared with primary samples, fulvic acids and polysaccharides were the predominant fractions of DOM at 20 days after organic degradation, indicating a higher aromatic degree of DOM. Meanwhile, the degradation rate of OH bonded by intermolecular H-bond of cellulose was faster than OH bonded by intra-molecular H-bond of cellulose, whereas the latter was more sensitive to microbial degradation. The degradation rate of phenolic hydroxyl C­O was the fastest, followed by aromatic COOH, carbohydrate C­O, and amide CO. Furthermore, the carbohydrate C­O was apt to be utilized preferentially by microorganisms. In sum, the structural change of various DOM in piggery wastewater was different during the process of organic degradation.

[Lower respiratory tract infection caused by influenza virus A and influenza virus B in Wenzhou, China: a clinical analysis of 366 children].

OBJECTIVE: To compare the epidemiological and clinical features of lower respiratory tract infection (LRTI) caused by influenza virus A (IVA) and influenza virus B (IVB) in children. METHODS: The clinical data of 366 children with LRTI caused by influenza virus (IV), who were hospitalized in Yuying Children′s Hospital of Wenzhou Medical University between 2010 and 2014, were analyzed retrospectively, and there were 272 cases caused by IVA and 94 cases caused by IVB. RESULTS: IV was mainly prevalent from December to March of the next year, with the predominance of IVA. There were small peaks of IVA prevalence in July or September every other year, and IVB was prevalent from December to March of the next year every other year. The children with LRTI caused by IVA alone had a significantly higher white blood cell (WBC) count and significantly higher percentages of children with increased WBC, abnormal serum sodium, and abnormal serum potassium than those caused by IVB alone (P<0.05). However, there were no significant differences in age, sex, underlying diseases, clinical manifestations, and co-infection rate with bacteria or atypical pathogens between the two groups (P>0.05). The rate of co-infection with respiratory syncytial virus (RSV) was significantly higher in the IVB group than in the IVA group (P<0.01). CONCLUSIONS: IVA is prevalent in winter and spring every year and has small peaks in summer every other year, while IVB is prevalent in winter and spring every other year. Compared with IVB, IVA causes more cases of increased WBC and electrolyte disturbance. The children infected with IVB are more likely to be co-infected with RSV. The children with LRTI caused by IVA and IVB have similar clinical manifestations.

Shock wave lithotripsy: the new phoenix?

INTRODUCTION: Following its introduction in 1980, shock wave lithotripsy (SWL) rapidly emerged as the first-line treatment for the majority of patients with urolithiasis. Millions of SWL therapies have since been performed worldwide, and nowadays, SWL still remains to be the least invasive therapy modality for urinary stones. During the last three decades, SWL technology has advanced in terms of shock wave generation, focusing, patient coupling and stone localization. The implementation of multifunctional lithotripters has made SWL available to urology departments worldwide. Indications for SWL have evolved as well. Although endoscopic treatment techniques have improved significantly and seem to take the lead in stone therapy in the western countries due to high stone-free rates, SWL continues to be considered as the first-line therapy for the treatment of most intra-renal stones and many ureteral stones. METHODS: This paper reviews the fundamentals of SWL physics to facilitate a better understanding about how a lithotripter works and should be best utilized. RESULTS: Advances in lithotripsy technology such as shock wave generation and focusing, advances in stone localization (imaging), different energy source concepts and coupling modalities are presented. Furthermore adjuncts to improve the efficacy of SWL including different treatment strategies are reviewed. CONCLUSION: If urologists make use of a more comprehensive understanding of the pathophysiology and physics of shock waves, much better results could be achieved in the future. This may lead to a renaissance and encourage SWL as first-line therapy for urolithiasis in times of rapid progress in endoscopic treatment modalities.

Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention.

Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due to aging and exercise as modulator of metabolism, a picture of how exercise delayed D-galactose (D-gal)-induced aging in a time-resolved manner was presented in this paper. The mapping of molecular changes in response to exercise has become increasingly accessible with the development of omics techniques. To explore the dynamic changes during exercise, the serum of rats and D-gal-induced aging rats before, during, and after exercise was analyzed by untargeted metabolomics. The variation of metabolites was monitored to reveal the specific response to D-gal-induced senescence and exercise in multiple pathways, especially the basal amino acid metabolism, including glycine serine and threonine metabolism, cysteine and methionine metabolism, and tryptophan metabolism. The homeostasis was disturbed by D-gal and maintained by exercise. The paper was expected to provide a theoretical basis for the study of anti-aging exercise.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.