Central Military Commission

As a physical factor therapeutic modality, the effect of a light therapy strongly depends on the dose, i.e. the light fluence $\left(\mathrm{J} / \mathrm{cm}^{2}\right)$, delivered to the target tissue. Especially, it is well known that there exists a biphasic dose response in light therapies, where neither too low nor too high doses can lead to effective and safe treatment. Moreover, in the existing research literatures, the reported effective doses may vary in a large range even in treating a same type of disease. This, on the one hand, may be attributed to the lack of precise control and measurement methods of the therapeutic light sources. On the other hand, despite the large number of studies on light therapies and the underlying photobiomodulation (PBM) mechanisms, the research on modeling the dose response in light therapies is still very rare, because of the tremendous challenge in identifying and quantifying the related chromophores and signaling pathways. In comparison, in the other physical factor therapies, e.g., photodynamic therapy, heavy ion therapy and proton therapy, mathematical dosimetric modeling has already become a much richer research literature. This mini review paper aims at surveying the recent research reports about the doses and dose-response models in light therapies, and thereby attempts to draw more attention to these important issues.

Macrophage apoptosis, along with inflammation in the interface membrane, has been demonstrated to be significant in the pathogenesis and development of particle-induced periprosthetic osteolysis and aseptic loosening. Additionally, the apoptosis of macrophages is considered an indicator of the resolution phase of inflammation and the transition to normal tissue healing. Therefore, targeting macrophages presents a promising strategy for both the prevention and therapeutic management of periprosthetic osteolysis. In this study, we explored the therapeutic potential of chemical chaperone 4-phenylbutyrate (4-PBA) as a pharmacological intervention aimed at modulating macrophage behaviors, particularly focusing on the processes of apoptosis, inflammation, and osteoclastogenesis in a murine model of TiAl6V4 nanoparticle (TiNP)-induced osteolysis. The results derived from in vivo studies conducted on the murine model provide compelling evidence that TiNPs could trigger osteolysis, activate inflammatory cell infiltration, and promote the differentiation of osteoclasts, accompanied by a notable rise in apoptosis at the osteolytic interface periosteum. The severity of TiNP-induced osteolysis, chaotic bone morphology, extensive bone erosion and destruction, occurrence of infiltrating inflammatory cells, and quantity of osteoclasts were attenuated following co-intervention with 4-PBA. Furthermore, the levels of apoptosis, in conjunction with apoptosis-regulated proteins Bcl-2 and Bax, were accentuated following 4-PBA co-intervention, indicating that the TiNP-induced osteolytic interface periosteum environment exhibited a greater propensity for apoptosis due to the pharmacological intervention of 4-PBA. Notably, the use of 4-PBA as a standalone treatment demonstrated comparatively low levels of toxicity and was deemed to be experimentally safe in mice. These findings indicated that 4-PBA may ameliorate the severity of particle-induced osteolysis by inhibiting the inflammatory response and promoting macrophage apoptosis in a manner that may be beneficial for therapeutic strategies. Thus, pharmacological intervention with 4-PBA appears to be a viable option for addressing osteolysis and aseptic loosening resulting from exposure to wear particles, combining efficacy in promoting apoptosis with a favorable safety profile.

Coptisine (COP), a naturally occurring alkaloid, is known for its diverse pharmacological effects and its supportive role in intestinal health. Despite this, the detailed mechanisms behind its therapeutic benefits are not yet fully understood. The objective of this study is to investigate the therapeutic potential of COP for the treatment of Ulcerative Colitis (UC) and to delineate the critical pathways by which it exerts its therapeutic effects. To assess COP's therapeutic effectiveness, mice were administered COP and monitored for clinical symptoms, activity, and disease activity index (DAI) changes. Intestinal histopathology, mucosal barrier function, and gut microbiota structure were evaluated, along with metabolic profiling, focusing on Prenol lipids in the colon to identify COP-induced metabolic shifts. Mice treated with COP exhibited significant relief from diarrhea and bleeding, along with increased activity and a marked reduction in DAI scores. Histopathological evaluation revealed a reduction in intestinal inflammation, and the intestinal mucosal barrier function was notably enhanced. The gut microbiota composition in COP-treated mice showed improvements. Additionally, the levels of Prenol lipids in the colon were elevated by COP treatment, which is crucial for the recovery of intestinal function. Our study demonstrates that COP effectively ameliorates colitis symptoms by modulating colon Prenol lipids metabolism, particularly under the influence of key bacterial species. The findings of this study provide novel insights into the therapeutic mechanisms of COP in the treatment of UC.

An accurate diagnosis is crucial for the clinical management of pancreatic cystic neoplasm (PCN). EUS-guided through-the-needle biopsy (EUS-TTNB) is a novel technique for improving the accuracy of PCN diagnosis. There is insufficient evidence about the efficacy of EUS-TTNB. This study aims to evaluate the feasibility and diagnostic performance of EUS-TTNB for PCN. Between June 2015 and July 2023, we prospectively enrolled 454 patients with a clinical concern for PCN in our database. After excluding those diagnosed with pancreatic cancer, pseudocysts, or other no-neoplasms, we assessed 326 patients with 329 cysts undergoing EUS-guided fine-needle-aspiration (EUS-FNA) or EUS-TTNB for evaluation. The primary indicators were tissue acquisition yield and diagnostic yield. The cyst characteristics (size, location, the presence of septation, mural nodule, and solid mass) and the number of biopsy samples were chosen for the analysis of factors associated with diagnostic performance. There were 220 (67.5%) females and 106 (32.5%) males, and the median patient age was 50 years (range, 18-88). There were 329 cysts sampled by FNA and 143 by TTNB. The median cyst size was 31.5 mm (range, 6.9-114.0). The diagnostic yields of FNA and TTNB were 35.7% (112/314) and 57.5% (73/127), respectively (P < 0.001). Special cyst types were diagnosed by TTNB in 58 (45.7%, 58/127) cysts, 19 of which had surgical pathology. Fifteen of 19 TTNB diagnoses were concordant with the surgical pathology. EUS-TTNB is an option to improve the diagnosis of PCN. Standardized procedures and appropriate indications for TTNB need to be studied.

Many studies have shown that total sleep deprivation (TSD) impairs the attention network, which includes three subcomponents as follows: alerting, orienting, and executive control. However, the specific attention network(s) damaged by TSD remains unclear. Twenty two participants were enrolled to complete the attention network test (ANT) before and after 36 h of TSD with simultaneous electroencephalography recordings. The repeated-measures analysis of variance of the response time (RT) suggested that the interaction effect between sleep conditions (before versus after TSD) and target congruence (incongruent versus congruent target) was significant; that is, the RT of the incongruent target was longer than that of the congruent target, whereas this difference disappeared after TSD. Furthermore, the interaction effect of sustained potential (SP) amplitude between the sleep conditions and target congruence was significant; that is, the incongruent target invoked a less positive sustained potential amplitude after than before TSD; whereas that invoked by the congruent target was not. TSD selectively impairs attention networks. TSD affects the executive control network the most, which is followed by the alerting network rather than the orienting network. This provides a new perspective for understanding how shortened sleep affects attention. No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.

Abstract The complexity of volcanic rocks presents challenges in seismic data quality and fine characterization of structural morphology, making velocity modeling difficult. In this study, we propose a velocity modeling method for volcanic rock areas that combines the use of amplitude envelope attribute and grid tomography inversion. By exploiting the strong reflection characteristics of volcanic rocks, the amplitude envelope attribute is employed to identify volcanic rock structures, eliminating the need for labor-intensive manual interpretation. The grid tomography inversion technique is then used to derive background velocity fields for all strata. These are further refined by incorporating the residual velocity fields of volcanic rocks through fusion and superposition. This integrated approach significantly improves the efficiency and accuracy of velocity modeling in complex volcanic rock areas, overcoming the limitations associated with conventional volcanic rock structural models and resulting in more accurate velocity inversion. The effectiveness and feasibility of the proposed method for velocity modeling in volcanic rock zone are demonstrated through the application of seismic data from an oilfield in eastern China. The results highlight the method's strong industrial application value.

Metformin is one of the first-line and widely-used drugs in patients with T2DM due to its safety profile, clinical efficacy and cheap cost. It is clearly that metformin has benefits on lowering hyperglycemia and diabetes-related complications in clinical use. However, the exact mechanisms of metformin in multiple therapies are still blurred. The classic effect of metformin is to reduce hepatic glucose production by inhibiting gluconeogenesis in liver and increase glucose utilization in peripheral tissues. Metformin targets mitochondrial respiratory chain complex I to specifically reduce reactive oxygen species generation to protect cells against oxidative stress-induced cell apoptosis. AMPK complex is a key factor in the action of metformin; however it is inconclusive that metformin activate AMPK directly or indirectly. Furthermore, the liver-centered mechanism of metformin has been challenged by that of gut microbiota alteration and GLP-1 secretion. Actually, more and more studies showed that metformin act on gut microbiota to exert anti-hyperglycemia effect. In addition, new emerging evidence showed that metformin has off-label function on bone metabolism, cancer inhibition and lifespan extension; however the underlying mechanism of such properties of metformin still remains elusive. Despite most of results are from cells in vitro and model organisms, clinical trials have been recruited by institutes around the world to verify the therapeutic effects of metformin in anti-tumor and anti-aging. Taken together, in this review we provide a new perspective on metformin and repurpose its novel and promising application in the therapy of cancer, bone fracture healing and age-related diseases.